for Journals by Title or ISSN
for Articles by Keywords
help

Publisher: Biomed Central Ltd.   (Total: 294 journals)

 A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z  

        1 2 | Last   [Sort by number of followers]   [Restore default list]

Showing 1 - 200 of 294 Journals sorted alphabetically
Acta Neuropathologica Communications     Open Access   (Followers: 1, SJR: 2.683, CiteScore: 5)
Acta Veterinaria Scandinavica     Open Access   (Followers: 2, SJR: 0.655, CiteScore: 1)
Addiction Science & Clinical Practice     Open Access   (Followers: 6, SJR: 1.224, CiteScore: 3)
Advances in Simulation     Open Access   (Followers: 4)
Agriculture & Food Security     Open Access   (Followers: 14, SJR: 0.575, CiteScore: 2)
AIDS Research and Therapy     Open Access   (Followers: 14, SJR: 1.08, CiteScore: 2)
Algorithms for Molecular Biology     Open Access   (Followers: 4, SJR: 1.333, CiteScore: 2)
Allergy, Asthma and Clinical Immunology     Open Access   (Followers: 25, SJR: 0.732, CiteScore: 2)
Alzheimer's Research & Therapy     Open Access   (Followers: 3, SJR: 2.449, CiteScore: 6)
Animal Biotelemetry     Open Access   (Followers: 1, SJR: 1.067, CiteScore: 2)
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 10, SJR: 1.104, CiteScore: 3)
Annals of General Psychiatry     Open Access   (Followers: 23, SJR: 0.784, CiteScore: 2)
Annals of Occupational and Environmental Medicine     Open Access   (Followers: 9, SJR: 0.452, CiteScore: 1)
Annals of Surgical Innovation and Research     Open Access   (Followers: 3, SJR: 0.328, CiteScore: 1)
Antimicrobial Resistance and Infection Control     Open Access   (Followers: 8, SJR: 1.573, CiteScore: 3)
Archives of Physiotherapy     Open Access   (Followers: 11)
Archives of Public Health     Open Access   (Followers: 12, SJR: 1.244, CiteScore: 3)
Arthritis Research & Therapy     Open Access   (Followers: 14, SJR: 2.154, CiteScore: 4)
Asia Pacific Family Medicine     Open Access   (Followers: 1, SJR: 0.538, CiteScore: 1)
Asthma Research and Practice     Open Access   (Followers: 1)
Basic and Clinical Andrology     Open Access   (SJR: 0.564, CiteScore: 2)
Behavioral and Brain Functions     Open Access   (Followers: 3, SJR: 0.986, CiteScore: 3)
Big Data Analytics     Open Access   (Followers: 25)
BioData Mining     Open Access   (Followers: 5, SJR: 0.982, CiteScore: 2)
Bioelectronic Medicine     Open Access  
Biological Procedures Online     Open Access   (SJR: 1.352, CiteScore: 4)
Biological Research     Open Access   (SJR: 0.654, CiteScore: 2)
Biology Direct     Open Access   (Followers: 7, SJR: 1.694, CiteScore: 3)
Biology of Mood & Anxiety Disorders     Open Access   (Followers: 5)
Biology of Sex Differences     Open Access   (Followers: 2, SJR: 1.902, CiteScore: 4)
Biomarker Research     Open Access   (Followers: 2)
Biomaterials Research     Open Access   (Followers: 4, SJR: 0.735, CiteScore: 3)
BioMedical Engineering OnLine     Open Access   (Followers: 7, SJR: 0.542, CiteScore: 2)
BioPsychoSocial Medicine     Open Access   (Followers: 7, SJR: 0.416, CiteScore: 1)
Biotechnology for Biofuels     Open Access   (Followers: 10, SJR: 1.899, CiteScore: 6)
BMC Anesthesiology     Open Access   (Followers: 17, SJR: 0.807, CiteScore: 2)
BMC Biochemistry     Open Access   (Followers: 14, SJR: 0.708, CiteScore: 2)
BMC Bioinformatics     Open Access   (Followers: 133, SJR: 1.479, CiteScore: 2)
BMC Biology     Open Access   (Followers: 60, SJR: 3.842, CiteScore: 5)
BMC Biophysics     Open Access   (Followers: 3, SJR: 0.682, CiteScore: 2)
BMC Biotechnology     Open Access   (Followers: 16, SJR: 1.012, CiteScore: 3)
BMC Cancer     Open Access   (Followers: 29, SJR: 1.464, CiteScore: 3)
BMC Cardiovascular Disorders     Open Access   (Followers: 21, SJR: 0.909, CiteScore: 2)
BMC Cell Biology     Open Access   (Followers: 48, SJR: 1.277, CiteScore: 3)
BMC Clinical Pathology     Open Access   (Followers: 7, SJR: 1.141, CiteScore: 3)
BMC Complementary and Alternative Medicine     Open Access   (Followers: 14, SJR: 0.858, CiteScore: 3)
BMC Dermatology     Open Access   (Followers: 13, SJR: 0.796, CiteScore: 2)
BMC Developmental Biology     Open Access   (Followers: 13, SJR: 1.43, CiteScore: 2)
BMC Ear, Nose and Throat Disorders     Open Access   (Followers: 1, SJR: 0.653, CiteScore: 2)
BMC Ecology     Open Access   (Followers: 20, SJR: 1.076, CiteScore: 2)
BMC Emergency Medicine     Open Access   (Followers: 17, SJR: 0.572, CiteScore: 1)
BMC Endocrine Disorders     Open Access   (Followers: 8, SJR: 0.965, CiteScore: 2)
BMC Evolutionary Biology     Open Access   (Followers: 73, SJR: 1.656, CiteScore: 3)
BMC Family Practice     Open Access   (Followers: 13, SJR: 1.137, CiteScore: 2)
BMC Gastroenterology     Open Access   (Followers: 15, SJR: 1.231, CiteScore: 3)
BMC Genetics     Open Access   (Followers: 25, SJR: 1.16, CiteScore: 3)
BMC Genomics     Open Access   (Followers: 85, SJR: 2.11, CiteScore: 4)
BMC Geriatrics     Open Access   (Followers: 14, SJR: 1.257, CiteScore: 3)
BMC Health Services Research     Open Access   (Followers: 15, SJR: 1.151, CiteScore: 2)
BMC Hematology     Open Access   (Followers: 3, SJR: 0.545, CiteScore: 1)
BMC Immunology     Open Access   (Followers: 10, SJR: 0.993, CiteScore: 3)
BMC Infectious Diseases     Open Access   (Followers: 18, SJR: 1.576, CiteScore: 3)
BMC Intl. Health and Human Rights     Open Access   (Followers: 6, SJR: 1.006, CiteScore: 2)
BMC Medical Education     Open Access   (Followers: 42, SJR: 0.765, CiteScore: 2)
BMC Medical Ethics     Open Access   (Followers: 21, SJR: 1.016, CiteScore: 2)
BMC Medical Genetics     Open Access   (Followers: 7, SJR: 1.109, CiteScore: 2)
BMC Medical Genomics     Open Access   (Followers: 4, SJR: 1.688, CiteScore: 3)
BMC Medical Imaging     Open Access   (Followers: 9, SJR: 0.536, CiteScore: 2)
BMC Medical Informatics and Decision Making     Open Access   (Followers: 23, SJR: 0.812, CiteScore: 2)
BMC Medical Physics     Open Access   (Followers: 6)
BMC Medical Research Methodology     Open Access   (Followers: 9, SJR: 2.221, CiteScore: 3)
BMC Medicine     Open Access   (Followers: 13, SJR: 4.219, CiteScore: 7)
BMC Microbiology     Open Access   (Followers: 13, SJR: 1.242, CiteScore: 3)
BMC Molecular Biology     Open Access   (Followers: 139, SJR: 1.216, CiteScore: 2)
BMC Musculoskeletal Disorders     Open Access   (Followers: 21, SJR: 0.951, CiteScore: 2)
BMC Nephrology     Open Access   (Followers: 9, SJR: 1.098, CiteScore: 3)
BMC Neurology     Open Access   (Followers: 22, SJR: 1.006, CiteScore: 2)
BMC Neuroscience     Open Access   (Followers: 15, SJR: 1.12, CiteScore: 2)
BMC Nursing     Open Access   (Followers: 23, SJR: 0.766, CiteScore: 2)
BMC Nutrition     Open Access   (Followers: 8)
BMC Obesity     Open Access   (Followers: 6)
BMC Ophthalmology     Open Access   (Followers: 14, SJR: 0.921, CiteScore: 2)
BMC Oral Health     Open Access   (Followers: 6, SJR: 0.867, CiteScore: 2)
BMC Palliative Care     Open Access   (Followers: 26, SJR: 1.105, CiteScore: 2)
BMC Pediatrics     Open Access   (Followers: 17, SJR: 1.278, CiteScore: 2)
BMC Pharmacology     Open Access   (Followers: 2)
BMC Pharmacology & Toxicology     Open Access   (Followers: 6, SJR: 0.785, CiteScore: 2)
BMC Physiology     Open Access   (Followers: 4, SJR: 0.936, CiteScore: 2)
BMC Plant Biology     Open Access   (Followers: 13, SJR: 1.887, CiteScore: 4)
BMC Pregnancy and Childbirth     Open Access   (Followers: 21, SJR: 1.427, CiteScore: 3)
BMC Proceedings     Full-text available via subscription   (Followers: 1, SJR: 0.302, CiteScore: 1)
BMC Psychiatry     Open Access   (Followers: 31, SJR: 1.346, CiteScore: 3)
BMC Psychology     Open Access   (Followers: 17, SJR: 0.817, CiteScore: 2)
BMC Public Health     Open Access   (Followers: 152, SJR: 1.337, CiteScore: 3)
BMC Pulmonary Medicine     Open Access   (Followers: 4, SJR: 1.373, CiteScore: 3)
BMC Research Notes     Open Access   (Followers: 4, SJR: 0.691, CiteScore: 2)
BMC Rheumatology     Open Access   (Followers: 1)
BMC Sports Science, Medicine and Rehabilitation     Open Access   (Followers: 28, SJR: 0.926, CiteScore: 2)
BMC Structural Biology     Open Access   (Followers: 8, SJR: 1.024, CiteScore: 2)
BMC Surgery     Open Access   (Followers: 10, SJR: 0.693, CiteScore: 2)
BMC Systems Biology     Open Access   (Followers: 12, SJR: 1.109, CiteScore: 2)
BMC Urology     Open Access   (Followers: 14, SJR: 0.853, CiteScore: 2)
BMC Veterinary Research     Open Access   (Followers: 16, SJR: 0.934, CiteScore: 2)
BMC Women's Health     Open Access   (Followers: 11, SJR: 0.931, CiteScore: 2)
BMC Zoology     Open Access   (Followers: 1)
Borderline Personality Disorder and Emotion Dysregulation     Open Access   (Followers: 10)
Breast Cancer Research     Open Access   (Followers: 15, SJR: 3.026, CiteScore: 6)
Burns & Trauma     Open Access   (Followers: 2)
Burns & Trauma     Open Access   (Followers: 10)
Cancer & Metabolism     Open Access   (Followers: 6)
Cancer Cell Intl.     Open Access   (Followers: 6, SJR: 1.13, CiteScore: 3)
Cancer Imaging     Open Access   (Followers: 2, SJR: 1.012, CiteScore: 3)
Cancers of the Head & Neck     Open Access   (Followers: 1)
Canine Genetics and Epidemiology     Open Access   (Followers: 1)
Cardio-Oncology     Open Access  
Cardiovascular Diabetology     Open Access   (Followers: 10, SJR: 2.157, CiteScore: 5)
Cardiovascular Ultrasound     Open Access   (Followers: 4, SJR: 0.812, CiteScore: 2)
Cell Communication and Signaling     Open Access   (Followers: 2, SJR: 2.211, CiteScore: 4)
Cell Division     Open Access   (Followers: 1, SJR: 2.445, CiteScore: 4)
Cellular & Molecular Biology Letters     Hybrid Journal   (Followers: 3)
Cerebellum & Ataxias     Open Access   (Followers: 1)
Child and Adolescent Psychiatry and Mental Health     Open Access   (Followers: 22, SJR: 0.901, CiteScore: 2)
Chinese Medicine     Open Access   (Followers: 2, SJR: 0.57, CiteScore: 2)
Chinese Neurosurgical J.     Open Access  
Chiropractic & Manual Therapies     Open Access   (Followers: 5, SJR: 0.599, CiteScore: 2)
Cilia     Open Access   (SJR: 0.732, CiteScore: 1)
Clinical and Molecular Allergy     Open Access   (Followers: 5, SJR: 0.933, CiteScore: 3)
Clinical and Translational Allergy     Open Access   (Followers: 2, SJR: 1.425, CiteScore: 4)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 20)
Clinical Sarcoma Research     Open Access  
Conflict and Health     Open Access   (Followers: 7, SJR: 1.851, CiteScore: 3)
Contraception and Reproductive Medicine     Open Access  
COPD Research and Practice     Open Access   (SJR: 0.755, CiteScore: 2)
Cost Effectiveness and Resource Allocation     Open Access   (Followers: 4, SJR: 0.888, CiteScore: 2)
Critical Care     Open Access   (Followers: 55, SJR: 2.48, CiteScore: 5)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 14)
Diabetology & Metabolic Syndrome     Open Access   (Followers: 7, SJR: 0.943, CiteScore: 2)
Diagnostic and Prognostic Research     Open Access  
Diagnostic Pathology     Open Access   (Followers: 7, SJR: 0.818, CiteScore: 2)
Disaster and Military Medicine     Open Access   (Followers: 4)
Emerging Themes in Epidemiology     Open Access   (Followers: 13, SJR: 1.003, CiteScore: 2)
Environmental Health     Open Access   (Followers: 11, SJR: 1.662, CiteScore: 4)
Environmental Health and Preventive Medicine     Open Access   (Followers: 3, SJR: 0.5, CiteScore: 1)
Epigenetics & Chromatin     Open Access   (Followers: 8, SJR: 3.767, CiteScore: 5)
European J. of Medical Research     Open Access   (Followers: 1, SJR: 0.55, CiteScore: 1)
European Review of Aging and Physical Activity     Open Access   (Followers: 8, SJR: 1.308, CiteScore: 4)
Experimental & Translational Stroke Medicine     Open Access   (Followers: 8, SJR: 0.98, CiteScore: 3)
Experimental Hematology & Oncology     Open Access   (Followers: 3, SJR: 0.842, CiteScore: 2)
Eye and Vision     Open Access   (Followers: 1)
Fertility Research and Practice     Open Access   (Followers: 2)
Fibrogenesis & Tissue Repair     Open Access   (SJR: 1.531, CiteScore: 4)
Fisheries and Aquatic Sciences     Open Access   (Followers: 2, SJR: 0.199, CiteScore: 0)
Flavour     Open Access   (Followers: 3)
Fluids and Barriers of the CNS     Open Access   (Followers: 2, SJR: 2.054, CiteScore: 5)
Frontiers in Zoology     Open Access   (Followers: 6, SJR: 1.597, CiteScore: 3)
Genes and Environment     Open Access   (Followers: 1, SJR: 0.516, CiteScore: 1)
Genetics Selection Evolution     Open Access   (Followers: 7, SJR: 1.745, CiteScore: 4)
Genome Biology     Open Access   (Followers: 31)
Genome Medicine     Open Access   (Followers: 5, SJR: 4.537, CiteScore: 7)
Global Health Research and Policy     Open Access   (Followers: 4)
Globalization and Health     Open Access   (Followers: 5, SJR: 1.262, CiteScore: 2)
Gut Pathogens     Full-text available via subscription   (Followers: 5, SJR: 1.066, CiteScore: 3)
Gynecologic Oncology Research and Practice     Open Access   (Followers: 1)
Harm Reduction J.     Open Access   (SJR: 1.445, CiteScore: 3)
Head & Face Medicine     Open Access   (Followers: 1, SJR: 0.62, CiteScore: 2)
Health and Quality of Life Outcomes     Open Access   (Followers: 14, SJR: 1.069, CiteScore: 3)
Health Research Policy and Systems     Open Access   (Followers: 13, SJR: 1.11, CiteScore: 2)
Hereditary Cancer in Clinical Practice     Open Access   (SJR: 0.848, CiteScore: 2)
Hereditas     Open Access   (Followers: 1, SJR: 0.278, CiteScore: 1)
Human Genomics     Open Access   (Followers: 2, SJR: 1.501, CiteScore: 3)
Human Resources for Health     Open Access   (Followers: 9, SJR: 1.301, CiteScore: 2)
Immunity & Ageing     Open Access   (Followers: 10, SJR: 1.218, CiteScore: 3)
Implementation Science     Open Access   (Followers: 18, SJR: 2.443, CiteScore: 4)
Infectious Agents and Cancer     Open Access   (SJR: 0.855, CiteScore: 2)
Infectious Diseases of Poverty     Open Access   (Followers: 1, SJR: 1.212, CiteScore: 3)
Inflammation and Regeneration     Open Access   (Followers: 1)
Intl. Breastfeeding J.     Open Access   (Followers: 22, SJR: 0.913, CiteScore: 3)
Intl. J. for Equity in Health     Open Access   (Followers: 6, SJR: 1.04, CiteScore: 2)
Intl. J. of Behavioral Nutrition and Physical Activity     Open Access   (Followers: 24, SJR: 2.626, CiteScore: 6)
Intl. J. of Health Geographics     Open Access   (Followers: 5, SJR: 1.385, CiteScore: 3)
Intl. J. of Mental Health Systems     Open Access   (Followers: 7, SJR: 0.721, CiteScore: 2)
Intl. J. of Pediatric Endocrinology     Open Access   (Followers: 10)
Intl. J. of Retina and Vitreous     Open Access   (Followers: 2)
Investigative Genetics     Open Access   (Followers: 1, SJR: 1.809, CiteScore: 3)
Irish Veterinary J.     Open Access   (Followers: 5, SJR: 0.657, CiteScore: 1)
Israel J. of Health Policy Research     Open Access   (SJR: 0.488, CiteScore: 1)
Italian J. of Pediatrics     Open Access   (Followers: 1, SJR: 0.685, CiteScore: 2)
J. for ImmunoTherapy of Cancer     Open Access   (Followers: 5, SJR: 2.798, CiteScore: 6)
J. of Angiogenesis Research     Open Access   (Followers: 2)
J. of Animal Science and Biotechnology     Open Access   (Followers: 4, SJR: 1.228, CiteScore: 3)
J. of Animal Science and Technology     Open Access   (Followers: 2)
J. of Biological Engineering     Open Access   (Followers: 3, SJR: 1.34, CiteScore: 4)
J. of Biological Research - Thessaloniki     Open Access   (SJR: 0.32, CiteScore: 2)
J. of Biomedical Semantics     Open Access   (Followers: 2, SJR: 0.952, CiteScore: 2)
J. of Cardiothoracic Surgery     Open Access   (Followers: 5, SJR: 0.607, CiteScore: 1)
J. of Cardiovascular Magnetic Resonance     Open Access   (Followers: 1, SJR: 2.292, CiteScore: 5)
J. of Clinical Movement Disorders     Open Access   (Followers: 3)
J. of Congenital Cardiology     Open Access   (Followers: 4)
J. of Diabetes and Metabolic Disorders     Open Access   (Followers: 8, SJR: 0.818, CiteScore: 2)
J. of Eating Disorders     Open Access   (Followers: 9, SJR: 0.693, CiteScore: 1)

        1 2 | Last   [Sort by number of followers]   [Restore default list]

Journal Cover
Journal of Experimental & Clinical Cancer Research
Journal Prestige (SJR): 2
Citation Impact (citeScore): 6
Number of Followers: 3  

  This is an Open Access Journal Open Access journal
ISSN (Print) 0392-9078 - ISSN (Online) 1756-9966
Published by Biomed Central Ltd. Homepage  [294 journals]
  • MAP17 predicts sensitivity to platinum-based therapy, EGFR inhibitors and
           the proteasome inhibitor bortezomib in lung adenocarcinoma

    • Abstract: Background The high incidence and mortality of lung tumours is a major health problem. Therefore, the identification both of biomarkers predicting efficacy for therapies in use and of novel efficacious therapeutic agents is crucial to increase patient survival. MAP17 (PDZK1IP1) is a small membrane-bound protein whose upregulation is reported as a common feature in tumours from diverse histological origins. Furthermore, MAP17 is correlated with tumour progression. Methods We assessed the expression of MAP17 in preclinical models, including cell lines and patient-derived xenografts (PDXs), assessing its correlation with sensitivity to different standard-of-care drugs in lung adenocarcinoma, as well as novel drugs. At the clinical level, we subsequently correlated MAP17 expression in human tumours with patient response to these therapies. Results We show that MAP17 expression is induced during lung tumourigenesis, particularly in lung adenocarcinomas, and provide in vitro and in vivo evidence that MAP17 levels predict sensitivity to therapies currently under clinical use in adenocarcinoma tumours, including cisplatin, carboplatin and EGFR inhibitors. In addition, we show that MAP17 expression predicts proteasome inhibitor efficacy in this context and that bortezomib, an FDA-approved drug, may be a novel therapeutic approach for MAP17-overexpressing lung adenocarcinomas. Conclusions Our results indicate a potential prognostic role for MAP17 in lung tumours, with particular relevance in lung adenocarcinomas, and highlight the predictive pot0065ntial of this membrane-associated protein for platinum-based therapy and EGFR inhibitor efficacy. Furthermore, we propose bortezomib treatment as a novel and efficacious therapy for lung adenocarcinomas exhibiting high MAP17 expression.
      PubDate: 2018-08-17
       
  • IL-33 facilitates proliferation of colorectal cancer dependent
           on COX2/PGE 2

    • Abstract: Background Interleukin-33 (IL-33) participates in various types of diseases including cancers. Previous studies of this cytokine in cancers mainly focused on its regulation on immune responses by which IL-33 modulated cancer progression. The IL-33 triggered signals in cancer cells remain unclear. Methods We analyzed IL-33 gene expression in human colorectal cancer (CRC) tissues and carried out gene enrichment analysis with TCGA Data Portal. We studied CRC proliferation in vivo by inoculating MC38 tumors in IL-33 transgenic mice. We investigated the cell proliferation in vitro with primary CRC cells isolated from fresh human CRC tissues, human CRC cell line HT-29 and mouse CRC cell line MC38. To evaluate the proliferation modulating effects of recombinant IL-33 incubation and other administrated factors, we measured tumor growth, colony formation, cell viability, and the expression of Ki67 and proliferating cell nuclear antigen (PCNA). We used several inhibitors, prostaglandin E2 (PGE2) neutralizing antibody, ST2 blocking antibody and specific shRNA expressing plasmid to study the pathway mediating IL-33-induced CRC proliferation. The IL-33 receptor ST2 in human CRC tissues was detected by immunohistochemistry staining and western blotting. The ST2-positive or negative subsets of primary CRC cells were acquired by flow cytometry sorting. Results We found that IL-33 expression was correlated with the gene signature of cell proliferation in 394 human CRC samples. The MC38 tumors grew more rapidly and the tumor Ki67 and PCNA were expressed at higher levels in IL-33 transgenic mice than in wild-type mice. IL-33 promoted cell growth, colony formation and expression of Ki67 and PCNA in primary CRC cells as well as CRC cell lines. IL-33 activated cycloxygenase-2 (COX2) expression and increased PGE2 production, whereas the COX2 selective inhibitor and PGE2 neutralizing antibody abolished the proliferation promoting effect of IL-33. ST2 blockade, ST2-negative sorting, NF-κB specific inhibitor and NF-κB specific shRNA (shP65) abrogated the COX2 induction caused by IL-33. Conclusion IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE2. IL-33 functions via its receptor ST2 and upregulates COX2 expression through NF-κB signaling. Understanding the IL-33 signal transduction in CRC cells provides potential therapeutic targets for clinical treatment.
      PubDate: 2018-08-17
       
  • KPNA2 promotes metabolic reprogramming in glioblastomas by regulation of
           c-myc

    • Abstract: Background Cancer cells maintain energy metabolism mainly by glycolysis, even under sufficient oxygen conditions. It gives cancer cells better growth advantages under complicated internal environment. KPNA2 is a novel oncogene that has received much attention in recent years, but the exact mechanisms of KPNA2 in tumorigenesis and progression are largely unknown. Especially its potential roles in the metabolic transformation of tumors still remain to be explored. Methods The expressions of KPNA2 in glioblastoma and normal human brain samples were analyzed by immunohistochemical analysis. The activities of key enzymes in glycolysis, the production of lactate acid and glucose uptake were investigated by colorimetry. GLUT-1 expression was measured by flow cytometry. CCK8 was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of KPNA2 in vivo. In addition, Co-IP, subcellular fractionation, western blot, immunofluorescence and luciferase assay were used to investigate the internal connection between KPNA2, c-myc and E2F1. Results In the present study, we found that KPNA2 was highly expressed in the glioma compared to the normal brain tissues. Level of KPNA2 was an independent predictor of prognosis in the glioma patients. Knockdown of KPNA2 in the glioblastoma cell lines U87 and U251 decreased deoxyglucose uptake, activities of the key glycolytic enzymes and lactate production. The level of oxidative phosphorylation (OXPHOS) was moderately decreased. Additioanlly, tumor proliferation and invasiveness were concomitantly downregulated. We have identified c-myc as a potential mediator of KPNA2. Aberrant expression of KPNA2 significantly changed the subcellular distribution of c-myc as well as its expression level. E2F1, another key cargo protein of KPNA2, was further identified to play a potential role in regulating the transcription of c-myc by KPNA2. Conclusions Our findings suggested that KPNA2, a potential tumor oncogene, performs its function in part via regulating cellular metabolism through c-myc signaling axis. It would provide a possible explanation for Warburg effect and thus offer a new perspective to the roles of KPNA2 in gliomagenesis.
      PubDate: 2018-08-16
       
  • Triptolide inhibits Epstein-Barr nuclear antigen 1 expression by
           increasing sensitivity of mitochondria apoptosis of nasopharyngeal
           carcinoma cells

    • Abstract: Background Epstein-Barr virus (EBV) is widely found in nasopharyngeal carcinoma (NPC) tissue and associated with poor prognosis of patients. EBV nuclear antigen 1 (EBNA1) is expressed in all NPC tumors and plays multiple biological roles in both virus and host cells. Triptolide is a natural product extracted from Tripterygium and shows anti-cancer activities. The goal of this work was to illustrate the anti-cancer effect of triptolide and elucidate a novel anti-apoptotic mechanism of EBNA1 in NPC cells encountered with triptolide. Methods In the present study, a CCK-8 assay was used to analyze the proliferation of NPC cells treated with triptolide in a dose- and time-dependent ways. Effects of triptolide on NPC cell cycle and apoptosis were investigated by flow cytometric analysis. EBNA1 expression in mRNA and protein levels was determined by quantitative real-time PCR and Western blot, respectively. Results Our results showed that triptolide effectively inhibited proliferation of NPC cells. Triptolide arrested NPC cell cycles in S phase and induced apoptosis through a caspase-9-dependent apoptosis pathway. Low-dose of triptolide reduced the half-life of EBNA1 and significantly decreased EBNA1 expression by promoting the process of proteasome-ubiquitin pathway. Over-expression of EBNA1, which was independent from EBV genome, effectively attenuated the apoptosis induced by triptolide. In addition, triptolide significantly inhibited proliferations of tumors induced by EBV-positive cells in vivo. Furthermore, EBNA1 were expressed in all NPC biopsies of Chinese patients. Conclusions In summary, our study provides the evidence that triptolide induces EBNA1 degradation and stimulates NPC apoptosis through mitochondria apoptotic pathway. In addition, EBNA1 assists NPC cells to resist triptolide-induced apoptosis through inhibiting caspase-9-dependent apoptotic pathway.
      PubDate: 2018-08-15
       
  • HJURP promotes hepatocellular carcinoma proliferation by destabilizing p21
           via the MAPK/ERK1/2 and AKT/GSK3β signaling pathways

    • Abstract: Background Holliday junction recognition protein (HJURP) has been implicated in many cancers including hepatocellular carcinoma (HCC). However, the underlying mechanism by which HJURP promotes HCC cell proliferation remains unclear. Methods RT-qPCR and immunohistochemistry were used to detect HJURP expression in HCC and adjacent tumor tissues and HCC cell lines. The localization of p21 were determined by immunofluorescence and western blot. Co-immunoprecipitation and western blot were used to validate the p21 stability and signaling pathways affected by HJURP. The effects of HJURP on HCC cell proliferation were assessed both in vivo and in vitro. The ERK1/2 pathway inhibitor U0126 and AKT pathway agonist SC-79 were used to treat HCC cell lines for further mechanistic investigations. Results HJURP expression was higher in HCC tissues than in para-tumor tissues. Moreover, ectopic HJURP expression facilitated the proliferation of HCC cells, whereas the depletion of HJURP resulted in decreased cell growth in vitro and in vivo. Furthermore, the effects of HJURP silencing were reversed by p21 knockdown. Likewise, p21 overexpression inhibited cell growth ability mediated by HJURP elevation. Mechanistically, HJURP destabilized p21 via the MAPK/ERK1/2 and AKT/GSK3β pathways, which regulated the nucleus-cytoplasm translocation and ubiquitin-mediated degradation of p21. Clinically, high HJURP expression was correlated with unfavorable prognoses in HCC individuals. Conclusions Our data revealed that HJURP is an oncogene that drives cell cycle progression upstream of p21 in HCC. These findings may provide a potential therapeutic and prognostic target for HCC.
      PubDate: 2018-08-15
       
  • Anti-inflammatory signaling by mammary tumor cells mediates prometastatic
           macrophage polarization in an innovative intraductal mouse model for
           triple-negative breast cancer

    • Abstract: Background Murine breast cancer models relying on intraductal tumor cell inoculations are attractive because they allow the study of breast cancer from early ductal carcinoma in situ to metastasis. Using a fully immunocompetent 4T1-based intraductal model for triple-negative breast cancer (TNBC) we aimed to investigate the immunological responses that guide such intraductal tumor progression, focusing on the prominent role of macrophages. Methods Intraductal inoculations were performed in lactating female mice with luciferase-expressing 4T1 mammary tumor cells either with or without additional RAW264.7 macrophages, mimicking basal versus increased macrophage-tumor cell interactions in the ductal environment. Imaging of 4T1-derived luminescence was used to monitor primary tumor growth and metastases. Tumor proliferation, hypoxia, disruption of the ductal architecture and tumor immune populations were determined immunohistochemically. M1- (pro-inflammatory) and M2-related (anti-inflammatory) cytokine levels were determined by Luminex assays and ELISA to investigate the activation state of the macrophage inoculum. Levels of the metastatic proteins matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor (VEGF) as well as of the immune-related disease biomarkers chitinase 3-like 1 (CHI3L1) and lipocalin 2 (LCN2) were measured by ELISA to evaluate disease progression at the protein level. Results Mice intraductally co-injected with macrophages showed severe splenomegaly with faster ductal breakthrough of tumor cells and increased metastases in axillary lymph nodes and lungs. These mice showed higher M1-related cytokines in the early disease stages (at 1 to 3 weeks post-inoculation) due to the pro-inflammatory nature of RAW264.7 macrophages with increased Ly6G-positive neutrophils and decreased anti-inflammatory macrophages in the tumor microenvironment. However, upon metastasis (at 5 weeks post-inoculation), a prominent increase in M2-related cytokine levels was detected and established a tumor microenvironment with similar immune populations and cytokine responses as in mice which received only 4T1 tumor cells. The observed tumor-associated immune responses and the increased metastasis were associated with significantly induced local and systemic levels of MMP-9, VEGF, CHI3L1 and LCN2. Conclusions The current experimental study with an innovative immunocompetent intraductal model for TNBC pinpoints towards a metastasis-supporting M1 to M2 macrophage polarization in the mammary ducts mediated by 4T1-derived signaling. We propose to explore this process as immunotherapeutic target.
      PubDate: 2018-08-15
       
  • MKRN2 inhibits migration and invasion of non-small-cell lung cancer by
           negatively regulating the PI3K/Akt pathway

    • Abstract: Background Makorin RING zinc finger-2 (MKRN2) belongs to the makorin RING zinc finger family and is a novel ubiquitin E3 ligase targeting the p65 subunit of NF-κB to negatively regulate inflammatory responses; however, the relationship between MKRN2 and tumorigenesis remains unclear. In this study, we clarified the role of MKRN2 in non-small cell lung cancer (NSCLC). Methods Tumor specimens collected from 261 NSCLC patients from 2013 to 2017 were retrieved from the Pathology Archive of the First Affiliated Hospital of China Medical University, and we performed assays to evaluate MKRN2 expression and to determine the impact of MKRN2 silencing and overexpression on NSCLC-cell migration and invasion. Results We demonstrated that MKRN2 expression was associated with lymph node metastasis, p-TNM stage, cancer-cell differentiation, and poor prognosis. By altering the expression of MKRN2 in selected cell lines, we found that MKRN2 inhibited cell migration and invasion through downregulation of the PI3K/Akt pathway. Conclusions These results suggested that MKRN2 inhibited NSCLC progression by reducing the metastatic potential of cancer cells. Our findings provide critical insight into the association of MKRN2 expression with favorable clinicopathological characteristics in NSCLC patients and suggested that MKRN2 plays a role in inhibiting NSCLC development.
      PubDate: 2018-08-13
       
  • Dual effect of DLBCL-derived EXOs in lymphoma to improve DC vaccine
           efficacy in vitro while favor tumorgenesis in vivo

    • Abstract: Background Exosomes derived from tumor cells (TEXs) are involved in both immune suppression, angiogenesis, metastasis and anticancer stimulatory, but the biological characteristics and role of diffuse large B cell lymphoma (DLBCL)-derived exosomes have been less investigated. Methods Exosomes (EXOs) were isolated from OCI-LY3, SU-DHL-16, and Raji cells and biological characteristics of EXOs were investigated using electron microscopy, flow cytometry analysis, and Western blot analysis. The protein expression of EXOs was determined by an antibody array. Next, the communication between EXOs and lymphoma cell, stromal cell, dendritic cells (DCs), and T cells was evaluated. Finally, effect of DLBCL TEXs on tumor growth in vivo was investigated. Results We demonstrated that EXOs derived from DLBCL cell lines displayed malignancy molecules such as c-Myc, Bcl-2, Mcl-1, CD19, and CD20. There was a different protein expression pattern between DLBCL TEXs and Burkitt lymphoma TEXs. DLBCL TEXs were easily captured by DCs and lymphoma cells, and mainly acted as an immunosuppressive mediator, evidenced by induction of apoptosis and upregulation of PD-1 in T cells. Furthermore, the TEXs stimulated not only cell proliferation, migration of stromal cells but also angiogenesis. As a result, the TEXs promoted tumor growth in vivo. On other hand, DLBCL TEXs did not induce apoptosis of DCs. After pulsed with the TEXs, DCs could stimulate clonal expansion of T cells, increase the secretion of IL-6 and TNFα, and decrease the production of immunosuppressive cytokine IL-4 and IL-10. The T cells from tumor bearing mice immunized by TEX were shown to possess superior antilymphoma potency relative to immunization of tumor lysates. Conclusions This study provides the framework for novel immunotherapies targeting TEXs in DLBCL.
      PubDate: 2018-08-13
       
  • TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR
           pathway to suppress tumorigenesis and metastasis in osteosarcoma, and
           predicts a favorable prognosis

    • Abstract: Background Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear. Methods We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing. Results We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models. Conclusions Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.
      PubDate: 2018-08-09
       
  • PCBP1 depletion promotes tumorigenesis through attenuation of p27 Kip1
           mRNA stability and translation

    • Abstract: Background Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. Methods We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay. Cell proliferation, cell cycle, tumorigenesis and cell apoptosis were also evaluated in ovary and colon cancer cell lines. The mechanism that PCBP1 affects p27 was analyzed by mRNA stability and ribosome profiling assays. We analyzed PCBP1 and p27 expression in ovary, colon and renal tumor samples and adjacent non-tumor tissues using RT-PCR, Western Blotting and immunohistochemistry. The prognostic significance of PCBP1 and p27 also analyzed using online databases. Results We identified cell cycle inhibitor p27Kip1 (p27) as a novel PCBP1-bound transcript. We then demonstrated that binding of PCBP1 to p27 3’UTR via its KH1 domain mainly stabilizes p27 mRNA, while enhances its translation to fuel p27 expression, prior to p27 protein degradation. The upregulated p27 consequently inhibits cell proliferation, cell cycle progression and tumorigenesis, whereas promotes cell apoptosis under paclitaxel treatment. Conversely, knockdown of PCBP1 in turn compromises p27 mRNA stability, leading to lower p27 level and tumorigenesis in vivo. Moreover, forced depletion of p27 counteracts the tumor suppressive ability of PCBP1 in the same PCBP1 over-expressing cells. Physiologically, we showed that decreases of both p27 mRNA and its protein expressions are well correlated to PCBP1 depletion in ovary, colon and renal tumor samples, independent of the p27 ubiquitin ligase Skp2 level. Correlation of PCBP1 with p27 is also found in the tamoxifen, doxorubincin and lapatinib resistant breast cancer cells of GEO database. Conclusion Our results thereby indicate that loss of PCBP1 expression firstly attenuates p27 expression at post-transcriptional level, and subsequently promotes carcinogenesis. PCBP1 could be used as a diagnostic marker to cancer patients.
      PubDate: 2018-08-07
       
  • Long noncoding RNA HEGBC promotes tumorigenesis and metastasis of
           gallbladder cancer via forming a positive feedback loop with IL-11/STAT3
           signaling pathway

    • Abstract: Background Gallbladder cancer (GBC) is a highly malignant cancer with poor prognosis. Several long noncoding RNAs (lncRNAs) have been reported to be involved in the tumorigenesis and progression of GBC. However, the expressions, clinical significances, and roles of most other lncRNAs in GBC are still unknown. Methods The differentially expressed lncRNAs in GBC were screened through re-analyzing the public available microarray datasets. The expression of lncRNA high expressed in gallbladder cancer (lncRNA-HEGBC) in GBC was measured by qRT-PCR. The correlations between HEGBC with clinicopathological characteristics and prognosis were analyzed by Pearson chi-square test and log-rank test. A series of in vitro and in vivo, gain-of and loss-of function assays were performed to investigate the roles of HEGBC in GBC cell proliferation, apoptosis, migration, tumor growth and metastasis. The interactions between HEGBC and IL-11/STAT3 signaling were explored using chromatin isolation by RNA purification (ChIRP), chromatin immunoprecipitation (ChIP), enzyme linked immunosorbent assay (ELISA), qRT-PCR, western blot, and luciferase reporter assays. Results We identified a novel lncRNA HEGBC, which is upregulated in GBC and positively associated with advanced TNM stages and poor prognosis of GBC patients. Overexpression of HEGBC increased GBC cell viability, inhibited GBC cell apoptosis, promoted GBC cell migration, and promoted GBC tumor growth and metastasis in vivo. Conversely, depletion of HEGBC decreased GBC cell viability, promoted GBC cell apoptosis, inhibited GBC cell migration, and inhibited GBC tumor growth and metastasis in vivo. Mechanistic investigations showed that HEGBC bound to the promoter of IL-11, increased IL-11 transcription, induced IL-11 autocrine, and activated IL-11/STAT3 signaling pathway. Furthermore, STAT3 also bound to the promoter of HEGBC and activated HEGBC expression. Thus, HEGBC/IL-11/STAT3 formed a positive regulatory loop in GBC. Depletion of IL-11 attenuated the oncogenic roles of HEGBC in GBC. Conclusions Our findings identified a novel lncRNA HEGBC, which is upregulated and indicts poor prognosis of GBC. HEGBC exerts oncogenic roles in GBC via forming a positive regulatory loop with IL-11/STAT3 signaling. Our data suggested that HEGBC could be a potential prognostic biomarker and therapeutic target for GBC.
      PubDate: 2018-08-07
       
  • Protease-activated receptor-1 (PAR1) promotes epithelial-endothelial
           transition through Twist1 in hepatocellular carcinoma

    • Abstract: Background Tumor cells transfer into endothelial cells by epithelial–endothelial transition (EET), which is characterized by vasculagenic mimicry (VM) in morphology. VM can change tumor microcirculation, progression, and metastasis. However, the molecular mechanisms of endothelial-like transition remain unclear. EET is a subtype of epithelial–mesenchymal transition (EMT). Twist1, a transcriptional regulatory factor of EMT, is an important factor that induces EET in hepatocellular carcinoma(HCC), but the upstream signal of Twist1 is unclear. Methods Expression plasmids, Ca mobilization, and three-dimensional cultures were evaluated. Western blot assay, reporter gene assay, and immunofluorescence staining were conducted. A murine xenograft model was established. Analyses of immunohistochemistry, patient samples, and complementary DNA (cDNA) microarrays were also performed. Results This study demonstrated that protease-activated receptor-1 (PAR1) can increase the expression of endothelial markers and enhance VM formation by upregulating Twist1 both in vitro and in vivo through thrombin binding. Thrombin not only activates PAR1 but also promotes PAR1 internalization in a time-dependent manner. Clinical pathological analysis further confirms that PAR1 expression is directly correlated with the endothelial marker expression, VM formation, and metastasis and indicates poor survival rate of patients with tumors. Conclusion PAR1 promotes EET through Twist1 in HCC.
      PubDate: 2018-08-06
       
  • Isoliquiritigenin suppresses human melanoma growth by targeting
           miR-301b/LRIG1 signaling

    • Abstract: Background Isoliquiritigenin (ISL), a natural flavonoid isolated from the root of licorice (Glycyrrhiza uralensis), has shown various pharmacological properties including anti-oxidant, anti-inflammatory and anti-cancer activities. MicroRNAs (miRNAs), a class of small non-coding RNAs, have been reported as post-transcriptional regulators with altered expression levels in melanoma. This study aims to investigate the anti-melanoma effect of ISL and its potential mechanism. Methods We investigated the effect of ISL on the proliferation and apoptosis of melanoma cell lines with functional assays, such as CCK-8 assay, colony formation assay and flow cytometry. The protein level of apoptosis related genes were measured by western blotting. High-throughput genome sequencing was used for screening differentially expressed miRNAs of melanoma cell lines after the treatment of ISL. We performed functional assays to determine the oncogenic role of miR-301b, the most differentially expressed miRNA, and its target gene leucine rich repeats and immunoglobulin like domains 1 (LRIG1), confirmed by bioinformatic analysis, luciferase reporter assay, western blotting and immunohistochemical assay in melanoma. Immunocompromised mouse models were used to determine the role of miR-301b and its target gene in melanoma tumorigenesis in vivo. The relationship between miR-301b and LRIG1 was further verified in GEO data set and tissue specimens. Results Functional assays indicated that ISL exerted significant growth inhibition and apoptosis induction on melanoma cells. MiR-301b is the most differentially expressed miRNA after the treatment of ISL and significantly downregulated. The suppressive effect of ISL on cell growth is reversed by ectopic expression of miR-301b. Intratumorally administration of miR-301b angomir enhances the inhibitory effect of ISL on tumor growth in vivo. Bioinformatic analysis showed that miR-301b may target LRIG1, miR-301b suppresses the luciferase activity of reporter constructs containing 3’UTR of LRIG1 as well as the expression level of LRIG1. And the anti-cancer effect of ISL is mitigated when LRIG1 is silenced in vivo and in vitro. Analysis of the melanoma samples obtained from patients shows that LRIG1 is negatively correlated with miR-301b. Conclusions ISL may inhibit the proliferation of melanoma cells by suppressing miR-301b and inducing its target LRIG1.
      PubDate: 2018-08-06
       
  • ANXA2 promotes esophageal cancer progression by activating MYC-HIF1A-VEGF
           axis

    • Abstract: Background ANXA2 (Annexin A2) is a pleiotropic calcium-dependent phospholipid binding protein that is abnormally expressed in various cancers. We previously found that ANXA2 is upregulated in esophageal squamous cell carcinoma (ESCC). This study was designed to investigate the functional significance of ANXA2 dysregulation and underlying mechanism in ESCC. Methods Proliferation, migration, invasion and metastasis assay were performed to examine the functional roles of ANXA2 in ESCC cells in vitro and in vivo. Real-time RT-PCR, immunoblotting, ChIP, reporter assay, confocal-immunofluorescence staining, co-immunoprecipitation and ubiquitination assay were used to explore the molecular mechanism underlying the actions of deregulated ANXA2 in ESCC cells. Results Overexpression of ANXA2 promoted ESCC cells migration and invasion in vitro and metastasis in vivo through activation of the MYC-HIF1A-VEGF cascade. Notably, ANXA2 phosphorylation at Tyr23 by SRC led to its translocation into the nucleus and enhanced the metastatic potential of ESCC cells. Phosphorylated ANXA2 (Tyr23) interacted with MYC and inhibited ubiquitin-dependent proteasomal degradation of MYC protein. Accumulated MYC directly potentiated HIF1A transcription and then activated VEGF expression. Correlation between these molecules were also found in ESCC tissues. Moreover, dasatinib in combination with bevacizumab or ANXA2-siRNA produced potent inhibitory effects on the growth of ESCC xenograft tumors in vivo. Conclusions This study provides evidence that highly expressed p-ANXA2 (Tyr23) contributes to ESCC progression by promoting migration, invasion and metastasis, and suggests that targeting the SRC-ANXA2-MYC-HIF1A-MYC axis may be an efficient strategy for ESCC treatment.
      PubDate: 2018-08-06
       
  • RIF1 promotes human epithelial ovarian cancer growth and progression via
           activating human telomerase reverse transcriptase expression

    • Abstract: Background Human telomerase reverse transcriptase (hTERT) is highly expressed in over 80% of tumors, including human epithelial ovarian cancer (EOC). However, the mechanisms through which hTERT is up-regulated in EOC and promotes tumor progression remain unclear. The aim of this study is to identify RIF1 as a novel molecular target that modulate hTERT signaling and EOC growth. Methods RIF1 expression in ovarian cancer, benign and normal ovarian tissues was examined by immunohistochemistry. The biological role of RIF1 was revealed by MTS, colony formation and sphere formation assays. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify RIF1 as a novel hTERT promoter-binding protein in EOC cells. The role of RIF1 on tumorigenesis in vivo was detected by the xenograft model. Results RIF1 expression is upregulated in EOC tissues and is closely correlated with FIGO stage and prognosis of EOC patients. Functionally, RIF1 knockdown suppressed the expression and promoter activity of hTERT and consequently inhibited the growth and CSC-like traits of EOC cells. RIF1 knockdown also inhibited tumorigenesis in xenograft model. RIF1 overexpression had the opposite effect. Luciferase reporter assay and ChIP assay verified RIF1 directly bound to hTERT promoter to upregulate its expression. The rescue experiments suggested hTERT overexpression rescued the inhibition of EOC cell growth and CSC-like traits mediated by RIF1 knockdown. Consistently, hTERT knockdown abrogated the RIF1-induced promotion of EOC cell growth and CSC-like traits. Conclusions RIF1 promotes EOC progression by activating hTERT and the RIF1/hTERT pathway may be a potential therapeutic target for EOC patients.
      PubDate: 2018-08-03
       
  • Reprogramming glioblastoma multiforme cells into neurons by protein kinase
           inhibitors

    • Abstract: Background Reprogramming of cancers into normal-like tissues is an innovative strategy for cancer treatment. Recent reports demonstrate that defined factors can reprogram cancer cells into pluripotent stem cells. Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor in humans. Despite multimodal therapy, the outcome for patients with GBM is still poor. Therefore, developing novel therapeutic strategy is a critical requirement. Methods We have developed a novel reprogramming method that uses a conceptually unique strategy for GBM treatment. We screened a kinase inhibitor library to find which candidate inhibitors under reprogramming condition can reprogram GBM cells into neurons. The induced neurons are identified whether functional and loss of tumorigenicity. Results We have found that mTOR and ROCK kinase inhibitors are sufficient to reprogram GBM cells into neural-like cells and “normal” neurons. The induced neurons expressed neuron-specific proteins, generated action potentials and neurotransmitter receptor-mediated currents. Genome-wide transcriptional analysis showed that the induced neurons had a profile different from GBM cells and were similar to that of control neurons induced by established methods. In vitro and in vivo tumorigenesis assays showed that induced neurons lost their proliferation ability and tumorigenicity. Moreover, reprogramming treatment with ROCK-mTOR inhibitors prevented GBM local recurrence in mice. Conclusion This study indicates that ROCK and mTOR inhibitors-based reprogramming treatment prevents GBM local recurrence. Currently ROCK-mTOR inhibitors are used as anti-tumor drugs in patients, so this reprogramming strategy has significant potential to move rapidly toward clinical trials.
      PubDate: 2018-08-02
       
  • Overexpression of the Kininogen-1 inhibits proliferation and induces
           apoptosis of glioma cells

    • Abstract: Background Glioma is the most common primary central nervous system tumor derived from glial cells. Kininogen-1 (KNG1) can exert antiangiogenic properties and inhibit proliferation of endothelial cells. The effect of KNG1 on the glioma is rarely reported, so our purpose in to explore its mechanism in glioma cells. Methods The differentially expressed genes (DEGs) were identified based on The Cancer Genome Atlas (TCGA) database. The KNG1-vector was transfected into the two glioma cells. The viability, apoptosis and cell cycle of glioma cells and microvessel density (MVD) were detected by cell counting kit-8 assay, flow cytometry and immunohistochemistry, respectively. The expression were measured by quantitative real-time PCR and Western blot, respectively. A tumor mouse model was established to determine apoptosis rate of brain tissue by terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL) analysis. Results KNG1 was identified as the core gene and lowly expressed in the glioma cells. Overexpression of KNG1 inhibited cell viability and angiogenesis of glioma cells. Overexpression of KNG1 promoted the apoptosis and G1 phase cell cycle arrest of glioma cells. Moreover, the expressions of VEGF, cyclinD1, ki67, caspase-3/9 and XIAP were regulated by overexpression of KNG1. In addition, overexpression of KNG1 inhibited the activity of PI3K/Akt. Furthermore, overexpression of KNG1 decreased the tumor growth and promoted the apoptosis of decreased by overexpression of KNG1 in vivo. . Conclusions Overexpression of KNG1 suppresses glioma progression by inhibiting the proliferation and promoting apoptosis of glioma cells, providing a therapeutic strategy for the malignant glioma.
      PubDate: 2018-08-02
       
  • Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and
           located within exosomes regulates endothelial monolayer permeability to
           promote tumor metastasis

    • Abstract: Background Recent studies show that exosomes are involved in intercellular communication and that abundant circular RNAs (circRNAs) are present within exosomes. However, whether these exosomal circRNAs contribute to tumor invasion and metastasis remains unclear, as do their associated mechanisms. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure the expression levels of circ-IARS in 85 pancreatic ductal adenocarcinoma (PDAC) tissues, plasma exosomes, and Hs 766 T, Hs 766 T-L2 and human microvascular vein endothelial (HUVECs) cells. RhoA, ZO-1 and RhoA-GTP levels were detected by qRT-PCR and western blotting (WB); RhoA activity analysis was also performed. Transwell assays were performed to examine changes in endothelial monolayer permeability, and immunofluorescence and WB were employed to evaluate F-actin expression and focal adhesion. Finally, an animal experiment was performed to detect the contribution of circ-IARS to cancer metastasis. Results circ-IARS expression was up-regulated in pancreatic cancer tissues and in plasma exosomes of patients with metastatic disease. Circ-IARS was found to enter HUVECs through exosomes and promote tumor invasion and metastasis. Circ-IARS expression was positively correlated with liver metastasis, vascular invasion, and tumor-node-metastasis (TNM) stage and negatively correlated with postoperative survival time. Overexpression of circ-IARS significantly down-regulated miR-122 and ZO-1 levels, up-regulated RhoA and RhoA-GTP levels, increased F-actin expression and focal adhesion, enhanced endothelial monolayer permeability, and promoted tumor invasion and metastasis. Conclusions circ-IRAS accesses HUVECs via exosomes derived from pancreatic cancer cells followed by increased endothelial monolayer permeability. Furthermore, this process promotes tumor invasion and metastasis. The results of this study suggest that the presence of circRNAs in exosomes may be important indicator for early diagnosis and prognostic prediction in PDAC.
      PubDate: 2018-07-31
       
  • High expression of Ras-related protein 1A promotes an aggressive phenotype
           in colorectal cancer via PTEN/FOXO3/CCND1 pathway

    • Abstract: Background Colorectal cancer (CRC) is a commonly diagnosed digestive malignancy worldwide. Ras-related protein 1A (RAP1A) is a member of the Ras superfamily of small GTPases and has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in CRC remains unclear. Method In this study, we firstly analyzed its expression and clinical significance in a retrospective cohort of 144 CRC patients. Then, cellular assays in vitro and in vivo were performed to clarify its biological role in CRC cells. Finally, microarray analysis was utilized to investigate the molecular mechanisms regulated by RAP1A in CRC progression. Results Firstly, RAP1A expression was abnormally higher in CRC tissues as compared with adjacent normal tissues, and significantly correlated tumor invasion. High RAP1A expression was an independent unfavourable prognostic factor for CRC patients. Combining RAP1A expression and preoperative CEA level contributed to a more accurate prognostic stratification in CRC patients. Secondly, knockdown of RAP1A dramatically inhibited the growth of CRC cells, while it was opposite for RAP1A overexpression. Finally, the microarray analysis revealed RAP1A promoted CRC growth partly through phosphatase and tensin homolog (PTEN)/forkhead box O3(FOXO3)/cyclin D1(CCND1) signaling pathway. FOXO3 overexpression could partly mimic the inhibitory effect of RAP1A knockdown in CRC growth. Moreover, FOXO3 overexpression inhibited CCND1 expression, but had no impact on RAP1A and PTEN expression. Conclusion RAP1A promotes CRC development partly through PTEN/FOXO3 /CCND1 signaling pathway. It has a great potential to be an effective clinical biomarker and therapeutic target for CRC patients.
      PubDate: 2018-07-31
       
  • Osteopontin alters DNA methylation through up-regulating DNMT1 and
           sensitizes CD133+/CD44+ cancer stem cells to 5 azacytidine in
           hepatocellular carcinoma

    • Abstract: Background In hepatocellular carcinoma (HCC), CD133+/CD44+ cells are one subgroup with high stemness and responsible for metastatic relapse and resistance to treatment. Our previous studies have demonstrated that osteopontin (OPN) plays critical roles in HCC metastasis. We further investigated the molecular mechanism underlying the role of OPN in regulating the stemness of HCC epigenetically and explored possible targeting strategy. Methods CD133+/CD44+ subgroup sorting from HCC cell lines and HCC tissues was used to investigate the effects of OPN knockdown on stemness. iTRAQ and MedIP-sequencing were applied to detect the protein profile and epigenetic modification of CD133+/CD44+ subgroup with or without OPN knockdown. The antitumor effects of 5 Azacytidine were examined in cultured HCC cells and patient derived xenograft (PDX) models. Results OPN was accumulated in CD133+/CD44+ subgroup of HCC cells. Knocking down OPN significantly inhibited the sphere formation and stemness-related genes expression, and delayed tumor initiation of CD133+/CD44+ subgroup of HCC cells. Employing MedIP-sequencing, dot blot and iTRAQ analyses of CD133+/CD44+ SCR and CD133+/CD44+ shOPN cells, we found that OPN knockdown leaded to reduction in DNA methylation with particular enrichment in CGI. Meanwhile, DNA (cytosine-5)-methyltransferase 1 (DNMT1), the main methylation maintainer, was downregulated via proteomics analysis, which mediated OPN altering DNA methylation. Furthermore, DNMT1 upregulation could partially rescue the properties of CD133+/CD44+ shOPN cells. Both in vitro and in vivo assays showed that CD133+/CD44+ cells with high OPN levels were more sensitive to DNA methylation inhibitor, 5 Azacytidine (5 Aza). The above findings were validated in HCC primary cells, a more clinically relevant model. Conclusions OPN induces methylome reprogramming to enhance the stemness of CD133+/CD44+ subgroup and provides the therapeutic benefits to DNMT1 targeting treatment in HCC.
      PubDate: 2018-07-31
       
 
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
 
Home (Search)
Subjects A-Z
Publishers A-Z
Customise
APIs
Your IP address: 54.81.110.186
 
About JournalTOCs
API
Help
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-