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Showing 1 - 98 of 98 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 10)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7)
Adipocyte     Open Access   (Followers: 1)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
American Journal of Experimental and Clinical Research     Open Access   (Followers: 4)
American Journal of Medical and Biological Research     Open Access   (Followers: 11)
Animal Models and Experimental Medicine     Open Access  
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 5)
Applied In Vitro Toxicology     Hybrid Journal   (Followers: 2)
Archives of Clinical and Experimental Medicine     Open Access  
Archives of Medical Research     Hybrid Journal   (Followers: 3)
Archives of Pathology & Laboratory Medicine     Full-text available via subscription   (Followers: 32)
Archives of Preventive Medicine     Open Access   (Followers: 3)
Biomedical Engineering     Hybrid Journal   (Followers: 3)
Bulletin of Experimental Biology and Medicine     Hybrid Journal  
Clinica Chimica Acta     Hybrid Journal   (Followers: 30)
Clinical & Experimental Metastasis     Hybrid Journal  
Clinical and Experimental Medical Journal     Full-text available via subscription   (Followers: 1)
Clinical and Experimental Medicine     Hybrid Journal   (Followers: 4)
Clinical Trials     Hybrid Journal   (Followers: 21)
Clinical Trials in Degenerative Diseases     Open Access  
Clinical Trials in Orthopedic Disorders     Open Access   (Followers: 1)
Current Medicine Research and Practice     Full-text available via subscription  
Current Research in Drug Discovery     Open Access   (Followers: 1)
Drug Design, Development and Therapy     Open Access   (Followers: 4)
Ecography     Hybrid Journal   (Followers: 27)
European Journal of Hospital Pharmacy : Science and Practice (EJHP)     Hybrid Journal   (Followers: 9)
European Journal of Medical Research     Open Access   (Followers: 1)
European Journal of Nanomedicine     Hybrid Journal   (Followers: 1)
Experimental & Molecular Medicine     Open Access   (Followers: 1)
Experimental Aging Research: An International Journal Devoted to the Scientific Study of the Aging Process     Hybrid Journal   (Followers: 3)
Experimental and Therapeutic Medicine     Full-text available via subscription   (Followers: 1)
Experimental Biology and Medicine     Hybrid Journal   (Followers: 3)
Expert Opinion on Drug Delivery     Hybrid Journal   (Followers: 20)
Frontiers in Laboratory Medicine     Open Access  
Frontiers in Medical Technology     Open Access   (Followers: 1)
IN VIVO     Full-text available via subscription   (Followers: 5)
International Archives of Biomedical and Clinical Research     Open Access  
International Journal of Experimental Pathology     Hybrid Journal   (Followers: 1)
International Journal of Health Research and Innovation     Open Access   (Followers: 2)
International Journal of Research in Medical Sciences     Open Access   (Followers: 7)
International Journal of Statistics in Medical Research     Hybrid Journal   (Followers: 5)
Journal of Cell Science & Therapy     Open Access   (Followers: 1)
Journal of Applied Biomaterials & Functional Materials     Hybrid Journal   (Followers: 1)
Journal of Biomedical and Clinical Research     Open Access  
Journal of Clinical Laboratory Analysis     Open Access   (Followers: 14)
Journal of Clinical Medicine and Research     Open Access  
Journal of Clinical Medicine Research     Open Access   (Followers: 4)
Journal of Clinical Trials     Open Access   (Followers: 6)
Journal of Current and Advance Medical Research     Open Access   (Followers: 2)
Journal of Current Medical Research and Practice     Open Access  
Journal of Current Research in Scientific Medicine     Open Access  
Journal of Drug Delivery and Therapeutics JDDT     Open Access   (Followers: 1)
Journal of Enzyme Inhibition and Medicinal Chemistry     Open Access   (Followers: 4)
Journal of Experimental & Clinical Medicine     Full-text available via subscription   (Followers: 1)
Journal of Experimental & Clinical Cancer Research     Open Access   (Followers: 2)
Journal of Experimental and Clinical Medicine     Open Access  
Journal of Experimental Medicine     Full-text available via subscription   (Followers: 46)
Journal of Experimental Pharmacology     Open Access   (Followers: 2)
Journal of Histotechnology     Hybrid Journal   (Followers: 2)
Journal of International Medical Research     Open Access   (Followers: 3)
Journal of Investigative Medicine High Impact Case Reports     Open Access  
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Muhammadiyah Medical Laboratory Technologist     Open Access  
Journal of Operating Department Practitioners     Full-text available via subscription   (Followers: 2)
Journal of the American Society of Cytopathology     Hybrid Journal   (Followers: 5)
Journal of Trace Elements in Medicine and Biology     Hybrid Journal   (Followers: 1)
Lab on a Chip     Full-text available via subscription   (Followers: 43)
Laboratory Investigation     Hybrid Journal   (Followers: 3)
Medical Devices & Sensors     Hybrid Journal  
Medical Image Analysis     Hybrid Journal   (Followers: 15)
Medical Instrumentation     Open Access  
Medical Laboratory Observer     Full-text available via subscription  
Medical Laboratory Technology Journal     Open Access  
Medicinal Chemistry Research     Hybrid Journal   (Followers: 12)
Medtech Insight     Full-text available via subscription   (Followers: 4)
Nanomedicine: Nanotechnology, Biology and Medicine     Hybrid Journal   (Followers: 7)
New Zealand Journal of Medical Laboratory Science     Full-text available via subscription   (Followers: 1)
Oriental Pharmacy and Experimental Medicine     Partially Free   (Followers: 3)
Pathology and Laboratory Medicine International     Open Access   (Followers: 7)
Physical Biology     Hybrid Journal   (Followers: 4)
Practical Laboratory Medicine     Open Access   (Followers: 2)
Proceedings of the Institution of Mechanical Engineers Part H: Journal of Engineering in Medicine     Hybrid Journal   (Followers: 3)
Prosthetics and Orthotics International     Hybrid Journal   (Followers: 10)
Pulse     Full-text available via subscription  
Qualitative Research in Medicine & Healthcare     Open Access  
Recent Advances in Biology and Medicine     Open Access  
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 43)
Reproduction     Full-text available via subscription   (Followers: 7)
Revista Peruana de Medicina Experimental y Salud P├║blica     Open Access  
Revista Romana de Medicina de Laborator     Open Access  
RSC Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
SA Pharmacist's Assistant     Open Access  
Savannah Journal of Medical Research and Practice     Full-text available via subscription  
SLAS Technology     Hybrid Journal   (Followers: 2)
Statistics in Medicine     Hybrid Journal   (Followers: 192)
Trends in Molecular Medicine     Full-text available via subscription   (Followers: 14)
Turkish Journal of Clinics and Laboratory     Open Access   (Followers: 1)
Similar Journals
Journal Cover
Journal of Experimental & Clinical Cancer Research
Journal Prestige (SJR): 2
Citation Impact (citeScore): 6
Number of Followers: 2  

  This is an Open Access Journal Open Access journal
ISSN (Print) 0392-9078 - ISSN (Online) 1756-9966
Published by BMC (Biomed Central) Homepage  [313 journals]
  • Down-regulated lncRNA SBF2-AS1 inhibits tumorigenesis and progression of
           breast cancer by sponging microRNA-143 and repressing RRS1

    • Abstract: Background Recently, the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in human diseases have been unveiled, this research was conducted to explore the impacts of lncRNA SET-binding factor 2-antisense RNA1 (SBF2-AS1), miR-143 and resistance to ralstonia solanacearum 1 (RRS1) on breast cancer (BC) development. Methods The expression of SBF2-AS1, miR-143 and RRS1 in BC tissues, as well as in MDA-MB-231 and MCF-7 cell lines were assessed. Subsequently, the cells were transfected with miR-143 mimics or/and silenced or overexpressed SBF2-AS1 plasmids, and their negative controls. Then the proliferation, colony formation ability, cell cycle arrest, apoptosis, invasion and migration of the cells were assessed through gain- and loss-of-function experiments. Furthermore, the tumor growth, ki-67 expression and apoptosis in vivo were observed by subcutaneous tumorigenesis in nude mice. Binding relation between SBF2-AS1 and miR-143, and that between miR-143 and RRS1 were confirmed. Results SBF2-AS1 and RRS1 were amplified, while miR-143 was reduced in BC tissues and cells. Reduced SBF2-AS1 and elevated miR-143 could repress the proliferation, invasion and migration via restraining RRS1 expression. Moreover, knockdown of SBF2-AS1 up-regulated miR-143 to promote the apoptosis of BC cells by downregulating RRS1, resulting in a prohibitive effect on the tumorigenesis and progression of BC. Results of in vivo experiments indicated that the inhibited SBF2-AS1 and overexpressed miR-143 could restrict BC cell proliferation and promote apoptosis, and decelerate tumor growth in xenografts. Conclusion We have discovered in this study that down-regulated SBF2-AS1 could inhibit tumorigenesis and progression of BC by up-regulation miR-143 and repressing RRS1, which provides basic therapeutic considerations for a novel target against BC.
      PubDate: 2020-01-17
  • Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK

    • Abstract: Background Our previous study showed Musashi2 (MSI2) promoted chemotherapy resistance and pernicious biology of pancreatic cancer (PC) by down-regulating Numb and p53. We further explored the novel molecular mechanism involving its oncogenic role in PC development. Methods We investigated the potential role and mechanism of MSI2 in EGF-induced EMT in PC in vitro and vivo. Results EGF enhanced EGFR (epidermal growth factor receptor) phosphorylation, induced EMT and activated ZEB1-ERK/MAPK signaling in 2 PC cells. However, MSI2 silencing reversed EGF stimulated function, including inhibiting EGF-promoted EMT-like cell morphology and EGF-enhanced cell invasion and migration. Meanwhile, MSI2 silencing inhibited EGF-enhanced EGFR phosphorylation at tyrosine 1068 and reversed EGF-induced change of the key proteins in EMT and ZEB1-ERK/MAPK signaling (ZEB1, E-cad, ZO-1, β-catenin, pERK and c-Myc). Additionally, MSI2 was co-stained and co-immunoprecipitated with ZEB1, pERK and c-Myc in PC cells by IF and co-IP, implying a close interaction between them. In vivo, MSI2 silencing inhibited pancreatic tumor size in situ and distant liver metastases. A close relationship of MSI2 with EMT and ZEB1-ERK/MAPK signaling were also observed in vivo and human PC samples, which coordinately promoted the poor prognosis of PC patients. Conclusions MSI2 promotes EGF-induced EMT in PC via ZEB1-ERK/MAPK signaling.
      PubDate: 2020-01-17
  • De-regulated STAT5A/miR-202-5p/USP15/Caspase-6 regulatory axis suppresses
           CML cell apoptosis and contributes to Imatinib resistance

    • Abstract: Background STAT5 plays an important role in the transformation of hematopoietic cells by BCR-ABL. However, the downstream target genes activated by STAT5 in chronic myeloid leukemia (CML) cells remain largely unclear. Here, we investigated the mechanistic functional relationship between STAT5A-regulated microRNA and CML cell apoptosis. Methods The expression of USP15, Caspase-6, STAT5A-regulated miR-202-5p and STAT5A was detected by qRT-PCR and Western blotting in CML cell lines and PBMCs of CML patients. Cell apoptosis was evaluated by flow cytometry. Both gain- and loss-of-function experiments were used to investigate the roles of USP15, miR-202-5p and STAT5A in CML. Luciferase reporter assay detected the effect of miR-202-5p on USP15 expression. Xenograft animal model was used to test the effect of anti-miR-202-5p and pimozide on K562 cell xenograft growth. Results USP15 expression was significantly downregulated in CML cell lines and PBMCs of CML patients. Depletion of USP15 increased, whereas overexpression of USP15 reduced the resistance of CML cells to Imatinib. Further, decreased deubiquitinating activity of USP15 by USP15 downregulation led to reduced caspase-6 level, thus attenuating CML cell apoptosis. Mechanistically, miR-202-5p was upregulated in K562G cells and negatively regulated USP15 expression by directly targeting USP15 3′-UTR. Correspondingly, upregulation of miR-202-5p enhanced the resistance of CML cells to Imatinib by inhibiting cell apoptosis. Importantly, STAT5A was upregulated in CML cells and directly activated miR-202-5p transcription by binding to the pre-miR-202 promoter. Pimozide induced CML cell apoptosis and significantly reduced K562 cell xenograft growth in vivo by blocking STAT5A/miR-202-5p/USP15/Caspase-6 regulatory axis. Conclusions we provide the first evidence that de-regulated STAT5A/miR-202-5p/USP15/Caspase-6 regulatory axis suppresses the apoptosis of CML cells, targeting this pathway might be a promising therapeutic approach for the treatment of CML.
      PubDate: 2020-01-17
  • Correction to: IL-33 facilitates proliferation of colorectal cancer
           dependent on COX2/PGE 2

    • Abstract: In the original publication of this manuscript [1], there are three errors in Fig. 1. The identified errors do not affect the conclusions of the work.
      PubDate: 2020-01-17
  • Correction to: ZNF326 promotes malignant phenotype of glioma by
           up-regulating HDAC7 expression and activating Wnt pathway

    • Abstract: In the original publication of this manuscript [1], the author mislabeled the CTL group and ZNF326 group in Fig. 2-I,J (MTT result). The revised Fig. 2 is shown below.
      PubDate: 2020-01-16
  • Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote
           pancreatic ductal adenocarcinoma (PDAC) progression

    • Abstract: Background Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal adenocarcinoma (PDAC) have not been revealed yet. Methods The expression of MOB1 and lysine demethylase 2B (KDM2B) in PDAC and adjacent normal pancreas tissues were measured. Also, the underlying mechanisms of altered MOB1 expression and its impact on PDAC biology were investigated. Results We revealed for the first time that MOB1 was decreased expression in PDAC and was a statistically significant independent predictor of poor survival, and restored expression of MOB1 suppressed the proliferation, migration and invasion of PDAC cells. Further studies demonstrated that KDM2B directly bound to the promoter region of MOB1, and suppressed the promoter activity of MOB1 and transcriptionally inhibited the MOB1 expression. Furthermore, KDM2B regulated Hippo pathway and promoted PDAC proliferation, migration and invasion via MOB1. Conclusion This study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression.
      PubDate: 2020-01-15
  • Correction to: DNMT3b/OCT4 expression confers sorafenib resistance and
           poor prognosis of hepatocellular carcinoma through IL-6/STAT3 regulation

    • Abstract: In the original publication of this article [1], labelling within Fig. 7a was incorrect. The updated figure is shown below, with ‘DMT1’ now corrected to read ‘DNMT1’.
      PubDate: 2020-01-13
  • Circular RNA circRHOBTB3 acts as a sponge for miR-654-3p inhibiting
           gastric cancer growth

    • Abstract: Background Circular RNAs (circRNAs) have recently emerged as a new family of noncoding RNAs that are involved in the causation and progression of various cancers. However, the roles of circRNAs in the tumorigenesis of gastric cancer (GC) are still largely unknown. Methods The expression profiles of circRNAs in GC were identified in open GEO database and were evaluated at the mRNA level in clinical GC samples compared with paired non-tumorous tissues. Kaplan-Meier survival curve was used to analyze the correlation of circRNA and patients’ prognosis. Subsequently, the circular structures of candidate circRNAs were validated by Sanger sequencing, divergent primer PCR, and RNase R treatments. Gain- and loss-of-function analyses were performed to evaluate the functional significance of it in GC initiation and progression. Dual-luciferase reporter and RNA pull-down assays were used to identify the microRNA (miRNA) sponge mechanism of circRNAs. Results The expression of circRHOBTB3 was lower in GC tissues and cell lines. Downregulation of circRHOBTB3 was significantly correlated with poor differentiation and unfavorable prognosis in patients with GC. Overexpression of circRHOBTB3 in GC cells led to decreased proliferation and induced G1/S arrest in vitro, accompanied with inhibited xenograft tumor growth in vivo, while the opposite effects were achieved in circRHOBTB3-silenced cells. Furthermore, we demonstrated that circRHOBTB3 acts as a sponge for miR-654-3p and verified that p21 is a novel target of miR-654-3p. Conclusion Taken together, this study revealed that circRHOBTB3 might function as competing endogenous RNA (ceRNA) for miR-654-3p, which could contribute to growth inhibition of GC through activating p21 signaling pathway. Our data suggested that circRHOBTB3 would serve as a novel promising diagnosis marker and therapeutic target for GC.
      PubDate: 2020-01-13
  • Complement C3 overexpression activates JAK2/STAT3 pathway and correlates
           with gastric cancer progression

    • Abstract: Background Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. Methods From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. Results C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor. Conclusions Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression. Trial registration, NCT02425930, Registered 1st August 2013.
      PubDate: 2020-01-13
  • C3a-C3aR signaling promotes breast cancer lung metastasis via modulating
           carcinoma associated fibroblasts

    • Abstract: Background Mounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown. Methods We performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer. Results C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models. Conclusions C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.
      PubDate: 2020-01-13
  • KDM4B facilitates colorectal cancer growth and glucose metabolism by
           stimulating TRAF6-mediated AKT activation

    • Abstract: Background Histone lysine demethylase 4B (KDM4B) has been implicated in various pathological processes and human diseases. Glucose metabolism is the main pattern of energy supply in cells and its dysfunction is closely related to tumorigenesis. Recent study shows that KDM4B protects against obesity and metabolic dysfunction. We realized the significant role of KDM4B in metabolism. However, the role of KDM4B in glucose metabolism remains unclear. Here, we sought to delineate the role and mechanism of KDM4B in glucose metabolism in colorectal cancer (CRC). Methods We first analyzed the role of KDM4B in glucose uptake and CRC growth. We then investigated the consequences of KDM4B inhibition on the expression of GLUT1 and AKT signaling, also explored the underlying mechanism. Finally, we detected the mechanism in vivo and assessed the potential correlation between the expression of KDM4B and CRC prognosis. Results We found that KDM4B promoted glucose uptake and ATP production by regulating the expression of GLUT1 via the AKT signaling pathway. KDM4B could interact with TRAF6 and promote TRAF6-mediated ubiquitination of AKT for AKT activation. Furthermore, we demonstrated that KDM4B was overexpressed in CRC specimens and high level of KDM4B was associated with a poor survival rate in CRC patients. Conclusions These findings reveal that KDM4B plays an important role in promoting CRC progression by enhancing glucose metabolism.
      PubDate: 2020-01-13
  • Targeting hypoxia in tumor: a new promising therapeutic strategy

    • Abstract: Low oxygen condition (hypoxia) is considered a hallmark of rapidly growing solid tumors. The presence of hypoxia renders tumor cells resistant to conventional chemo- and radio-therapy selecting a more malignant and invasive phenotype, and playing a negative role in patient prognosis. This commentary wishes to recognize the 2019 Nobel Prize in Medicine awarded to three physicians-scientists, Prof. William G. Kaelin Jr., Prof. Sir Peter J. Ratcliffe, and Prof. Gregg L. Semenza, for their discovery of the mechanisms mediating cell ability to sense and adapt to changes in oxygen availability. Their studies established the basis for our understanding of the role of hypoxia in a variety of diseases, including anemia, renal failure, cardiovascular disease, metabolic diseases, and cancer, paving the way for new promising therapeutic strategies through the development of drugs that can either activate or block the oxygen-sensing machinery.
      PubDate: 2020-01-10
  • lncTUG1/miR-144-3p affect the radiosensitivity of esophageal squamous cell
           carcinoma by competitively regulating c-MET

    • Abstract: Background Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers and affect the response to radiotherapy. This study focused on clarifying the underlying mechanism by which lncTUG1 affects the radiosensitivity of esophageal squamous cell carcinoma (ESCC). Methods lncTUG1, miR-144-3p and MET expression levels were detected in ESCC tissues and cells by qRT-PCR. Western blotting was used to examine the protein levels of MET, p-AKT and EGFR. The dual-luciferase reporter system and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between lncTUG1 and miR-144-3p or miR-144-3p and MET. MTT, colony formation and flow cytometry assays were applied to examine the behavioral changes in EC9706 and KYSE30 cells. Results lncTUG1 was upregulated in ESCC cells and tissues, and lncTUG1 expression was associated with an advanced pathological stage. The bioinformatics analysis revealed that lncTUG1 could specifically bind to miR-144-3p, which was downregulated in ESCC. There was a negative correlation between lncTUG1 and miR-144-3p. LncTUG1 inhibition retarded proliferation and colony formation and induced apoptosis in ESCC cells. Moreover, lncTUG1 knockdown dramatically improved the effect of radiotherapy on ESCC development both in vivo and in vitro. Furthermore, MET was revealed as a downstream target of miR-144-3p and is downregulated by it. LncTUG1 promoted the progression of ESCC and elevated radiotherapy resistance in ESCC cells, accompanied by a high level of MET expression. Moreover, we found that knockdown of lncTUG1 enhanced the radiosensitivity of ESCC cells via the p-AKT signaling pathway. Conclusion Our results indicate that lncTUG1 enhances the radiotherapy resistance of ESCC by lowering the miR-144-3p level and modulating the MET/EGFR/AKT axis.
      PubDate: 2020-01-09
  • A pre-existing population of ZEB2 + quiescent cells with stemness and
           mesenchymal features dictate chemoresistance in colorectal cancer

    • Abstract: Background Quiescent/slow cycling cells have been identified in several tumors and correlated with therapy resistance. However, the features of chemoresistant populations and the molecular factors linking quiescence to chemoresistance are largely unknown. Methods A population of chemoresistant quiescent/slow cycling cells was isolated through PKH26 staining (which allows to separate cells on the basis of their proliferation rate) from colorectal cancer (CRC) xenografts and subjected to global gene expression and pathway activation analyses. Factors expressed by the quiescent/slow cycling population were analyzed through lentiviral overexpression approaches for their ability to induce a dormant chemoresistant state both in vitro and in mouse xenografts. The correlation between quiescence-associated factors, CRC consensus molecular subtype and cancer prognosis was analyzed in large patient datasets. Results Untreated colorectal tumors contain a population of quiescent/slow cycling cells with stem cell features (quiescent cancer stem cells, QCSCs) characterized by a predetermined mesenchymal-like chemoresistant phenotype. QCSCs expressed increased levels of ZEB2, a transcription factor involved in stem cell plasticity and epithelial-mesenchymal transition (EMT), and of antiapototic factors pCRAF and pASK1. ZEB2 overexpression upregulated pCRAF/pASK1 levels resulting in increased chemoresistance, enrichment of cells with stemness/EMT traits and proliferative slowdown of tumor xenografts. In parallel, chemotherapy treatment of tumor xenografts induced the prevalence of QCSCs with a stemness/EMT phenotype and activation of the ZEB2/pCRAF/pASK1 axis, resulting in a chemotherapy-unresponsive state. In CRC patients, increased ZEB2 levels correlated with worse relapse-free survival and were strongly associated to the consensus molecular subtype 4 (CMS4) characterized by dismal prognosis, decreased proliferative rates and upregulation of EMT genes. Conclusions These results show that chemotherapy-naive tumors contain a cell population characterized by a coordinated program of chemoresistance, quiescence, stemness and EMT. Such population becomes prevalent upon drug treatment and is responsible for chemotherapy resistance, thus representing a key target for more effective therapeutic approaches.
      PubDate: 2020-01-08
  • Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth
           and metastasis

    • Abstract: Background Recent evidence indicates that metformin inhibits mammalian cancer growth and metastasis through the regulation of microRNAs. Metformin regulates miR-381 stability, which plays a vital role in tumor progression. Moreover, increased YAP expression and activity induce non-small cell lung cancer (NSCLC) tumor growth and metastasis. However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown. Methods Levels of RNA and protein were analyzed using qPCR, western blotting and immunofluorescence staining. Cellular proliferation was detected using a CCK8 assay. Cell migration and invasion were analyzed using wound healing and transwell assays. Promoter activity and transcription were investigated using the luciferase reporter assay. Chromatin immunoprecipitation was used to detect the binding of YAP to the promoter of Snail. The interaction between miR-381 and the 3′UTR of YAP mRNA was analyzed using the MS2 expression system and co-immunoprecipitation with biotin. Results We observed that miR-381 expression is negatively correlated with YAP expression and plays an opposite role to YAP in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. The miR-381 function as a tumor suppressor was significantly downregulated in lung cancer tissue specimens and cell lines, which decreased the expression of its direct target YAP. In addition, metformin decreased cell growth, migration, invasion, and EMT via up-regulation of miR-381. Moreover, YAP, which functions as a co-transcription factor, enhanced NSCLC progression and metastasis by upregulation of Snail. Snail knockdown downregulated the mesenchymal marker vimentin and upregulated the epithelial marker E-cadherin in lung cancer cells. Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT. Conclusions Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis. Thus, we believe that the miR-381-YAP-Snail signal axis may be a suitable diagnostic marker and a potential therapeutic target for lung cancer.
      PubDate: 2020-01-06
  • LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by
           competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression
           and activating ERK signaling pathway

    • Abstract: Background LncRNA LINC00662 is closely related to the occurrence and development of cancer. This study aims to explore the effect of LINC00662 on colon cancer tumor growth and metastasis and its molecular mechanism. Methods CCK8, colony formation, transwell, scratch wound, TUNEL, flow cytometry, RT-PCR, western blotting and immunohistochemistry assays were used to detect the proliferation, apoptosis, invasion and migration of colon cancer cell and mRNA and protein expressions. Luciferase reporter and RNA pull down assays were used to detect the combination of LINC00662 and miR-340-5p or IL22 and the combination of miR-340-5p and CLDN8/IL22. Co-immunoprecipitation were used to detect the co-expression of CLDN8 and IL22 in colon cell lines. The targets of LINC00662 were predicated by Starbase v2.0. The target genes of miR-340-5p were predicated by miRDB and TargetScan. GO and KEGG enrichment analysis were performed by DAVID website. Results LINC00662 was up-regulation in colon cancer tissues and cell lines. Univariate Cox regression analysis showed that the LINC00662 expression level was related to the poor prognosis. LINC00662-WT and miR-340-5p mimics co-transfection depressed luciferase activity and IL22/CLDN8-WT and miR-340-5p inhibitors co-transfection memorably motivated luciferase activity. LINC00662 overexpression promoted cell proliferation, invasion and migration, and inhibited cell apoptosis in colon cancer. In vivo xenograft studies in nude mice manifested that LINC00662 overexpression prominently accelerate tumor growth. There was an opposite reaction in the biological functions of colon cells and tumor growth between LINC00662 overexpression and LINC00662 inhibition in vitro and in vivo. The functions of miR-340-5p mimics regulating the biological functions of colon cells and tumor growth were consistent with those of LINC00662 inhibition. CLDN8 and IL22, as target genes of miR-340-5p, reversed the functions of LINC00662 affecting the biological functions of colon cells and the protein levels of Bax, Bcl-2, XIAP, VEGF, MMP-2, E-cadherin and N-cadherin. Co-immunoprecipitation experiments indicated that CLDN8 directly interact with IL22 in colon cell lines. LINC00662 regulated CLDN8 and IL22 expressions and the activation of ERK signaling pathway via targeting miR-340-5p. Conclusion LINC00662 overexpression promoted the occurrence and development of colon cancer by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway.
      PubDate: 2020-01-03
  • MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting
           Neuropilin 1

    • Abstract: Background Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance. Methods Using three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons’ correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells. Results We observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells. Conclusions These data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells. Thus, the combination of Olaparib with miRNA-based therapy may represent a promising treatment for drug resistant OC, and our data may help in designing novel precision medicine trials for optimizing the clinical use of PARPi.
      PubDate: 2020-01-02
  • MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem
           cells improve hepatocellular carcinoma chemosensitivity through mTOR

    • Abstract: Background MiR-199a-3p (miR-199a) can enhance the chemosensitivity of hepatocellular carcinoma (HCC). Because of the easy degradation of miRNA by direct infusion, effective vehicle-mediated delivery of miR-199a may represent a new strategy for improving HCC chemotherapy. Considering mesenchymal stem cell (MSC)-derived exosomes as promising natural nanovectors for drug and molecule delivery, we aimed to determine whether exosomes from adipose tissue-derived MSCs (AMSCs) could be used to deliver miR-199a and improve HCC chemosensitivity. Methods MiR-199a-modified AMSCs (AMSC-199a) were constructed by miR-199a lentivirus infection and puromycin selection. MiR-199-modified exosomes (AMSC-Exo-199a) were isolated from the supernatant of AMSC-199a and were assessed by transmission electron microscopy, nanoparticle tracking analysis, and flow cytometry analysis. The expression levels of miR-199a in HCC samples, AMSCs, exosomes, and HCC cells were quantified by real-time PCR. The effects of AMSC-Exo-199a on HCC chemosensitivity were determined by cell proliferation and apoptosis assays and by i.v. injection into orthotopic HCC mouse models with doxorubicin treatment. MTOR, p-4EBP1 and p-70S6K levels in HCC cells and tissues were quantified by Western blot. Results AMSC-Exo-199a had the classic characteristics of exosomes and could effectively mediate miR-199a delivery to HCC cells. Additionally, AMSC-Exo-199a significantly sensitized HCC cells to doxorubicin by targeting mTOR and subsequently inhibiting the mTOR pathway. Moreover, i.v.-injected AMSC-Exo-199a could distribute to tumor tissue and markedly increased the effect of Dox against HCC in vivo. Conclusions AMSC-Exo-199a can be an effective vehicle for miR-199a delivery, and they effectively sensitized HCC to chemotherapeutic agents by targeting mTOR pathway. AMSC-Exo-199a administration may provide a new strategy for improving HCC chemosensitivity.
      PubDate: 2020-01-02
  • Musashi2 contributes to the maintenance of CD44v6+ liver cancer stem cells
           via notch1 signaling pathway

    • Abstract: Background Liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) development, metastasis, and drug resistance. MSI2 and Notch1 signaling are involved in the maintenance of CSCs. However, it is unknown whether MSI2 and Notch1 are involved in the maintenance of CD44v6+ LCSCs. Therefore, we investigated the clinical significance and function of MSI2 and its relationship with Notch1 signaling in the maintenance of stemness properties in CD44v6+ LCSCs. Methods The expression of MSI2 and CD44v6 were detected by fresh specimens and a HCC tissue microarray. The tissue microarray containing 82 HCC samples was used to analyze the correlation between CD44v6 and MSI2. CD44v6+/− cells were isolated using microbeads sorting. We explored the roles of MSI2 and Notch1 signaling in CD44v6+ LCSCs by sphere formation assay, transwell assay, clone formation assay in vitro, and xenograft tumor models in vivo. A Notch RT2 PCR Array, Co-immunoprecipitation, and RNA-immunoprecipitation were used to further investigate the molecular mechanism of MSI2 in activating Notch1 signaling. Results Here, we found MSI2 expression was positively correlated with high CD44v6 expression in HCC tissues, and further correlated with tumor differentiation. CD44v6+ cells isolated from HCC cell lines exhibited increased self-renewal, proliferation, migration and invasion, resistance to Sorafenib and tumorigenic capacity. Both MSI2 and Notch1 signaling were elevated in sorted CD44v6+ cells than CD44v6- cells and played essential roles in the maintenance of stemness of CD44v6+ LCSCs. Mechanically, MSI2 directly bound to Lunatic fringe (LFNG) mRNA and protein, resulting in Notch1 activation. Conclusions Our results demonstrated that MSI2 maintained the stemness of CD44v6+ LCSCs by activating Notch1 signaling through the interaction with LFNG, which could be a potential molecular target for stem cell-targeted therapy for liver cancer.
      PubDate: 2019-12-30
  • CircNFIX promotes progression of glioma through regulating miR-378e/RPN2

    • Abstract: Background Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. Methods GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. Results The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. Conclusion Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.
      PubDate: 2019-12-30
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762

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