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Journal of Cancer
Journal Prestige (SJR): 1.159  Citation Impact (citeScore): 3 Number of Followers: 9  Open Access journalISSN (Print) 1837-9664 Published by Ivyspring International Publisher  [3 journals]
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- HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells
through Sox2 under hypoxic conditions
Authors: Pan Wang; Sheng Gong, Bin Liao, Jinyu Pan, Junwei Wang, Dewei Zou, Lu Zhao, Shuanglong Xiong, Yangmin Deng, Qian Yan, Nan Wu
Pages: 1 - 14
Abstract: Objective: Our previous study showed that glioma stem-like cells could be induced to undergo dedifferentiation under hypoxic conditions, but the mechanism requires further study. HIF1α and HIF2α are the main molecules involved in the response to hypoxia, and Sox2, as a retroelement, plays an important role in the formation of induced pluripotent stem cells, especially in hypoxic microenvironments. Therefore, we performed a series of experiments to verify whether HIF1α, HIF2α and Sox2 regulated glioma cell dedifferentiation under hypoxic conditions.Materials and methods: Sphere formation by single glioma cells was observed, and CD133 and CD15 expression was compared between the normoxic and hypoxic groups. HIF1α, HIF2α, and Sox2 expression was detected using the CGGA database, and the correlation among HIF1α, HIF2α and Sox2 levels was analyzed. We knocked out HIF1α, HIF2α and Sox2 in glioma cells and cultured them under hypoxic conditions to detect CD133 and CD15 expression. The above cells were implanted into mouse brains to analyze tumor volume and survival time.Results: New spheres were formed from single glioma cells in 1% O2, but no spheres were formed in 21% O2. The cells cultured in 1% O2 highly expressed CD133 and CD15 and had a lower apoptosis rate. The CGGA database showed HIF1α and HIF2α expression in glioma. Knocking out HIF1α or HIF2α led to a decrease in CD133 and CD15 expression and inhibited sphere formation under hypoxic conditions. Moreover, tumor volume and weight decreased after HIF1α or HIF2α knockout with the same temozolomide treatment. Sox2 was also highly expressed in glioma, and there was a positive correlation between the HIF1α/HIF2α and Sox2 expression levels. Sox2 was expressed at lower levels after HIF1α or HIF2α was knocked out. Then, Sox2 was knocked out, and we found that CD133 and CD15 expression was decreased. Moreover, a lower sphere formation rate, higher apoptosis rate, lower tumor formation rate and longer survival time after temozolomide treatment were detected in the Sox2 knockout cells.Conclusion: In a hypoxic microenvironment, the HIF1α/HIF2α-Sox2 network induced the formation of glioma stem cells through the dedifferentiation of differentiated glioma cells, thus promoting glioma cell chemoresistance. This study demonstrates that both HIF1α and HIF2α, as genes upstream of Sox2, regulate the malignant progression of glioma through dedifferentiation.
Citation: Journal of Cancer
PubDate: 2022
Issue No: Vol. 13, No. 1 (2022)
- The prognostic value of baseline hematological parameters of peripheral
blood in metastatic gastric cancer treated with apatinib
Authors: Jin-Ru Yang; Dan-Yang Zhou, Ying Wu, Ying Zhu, Zhen-Yu Lin, Tao Zhang, Dan-Dan Yu
Pages: 15 - 20
Abstract: Background: There is strong evidence that apatinib is effective in the treatment of third- or later-line advanced metastatic gastric cancer (mGC). Hematology prediction index is a convenient and cheap method to predict the prognosis of disease. However, the prognosis of baseline hematological parameters of peripheral blood, such as neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen 125 (CA125) and albumin (ALB) on mGC treated with apatinib have not been identified.Methods: We retrospectively analyzed mGC received apatinib between 1 January 2014 and 30 June 2021. Survival analyses were performed using the Kaplan-Meier method and Cox-proportional hazards model.Results: A total of 117 patients were included in this study. The cutoff value of NLR, CA125 and ALB was 2.25, 19.24 U/ml and 37.60 g/L, respectively. The disease control rates (DCR) in the high and low NLR groups were 52.94% and 73.47% (P=0.024); 48.28% and 74.58% (P=0.003) in high and low CA125 groups; 72.97% and 41.86% (P=0.001) in high and low ALB groups. By survival analysis, increasing NLR (P=0.003), CA125 (P
Citation: Journal of Cancer
PubDate: 2022
Issue No: Vol. 13, No. 1 (2022)
- Identification and Validation of a Novel 2-LncRNAs Signature Associated
with m6A Regulation in Colorectal Cancer
Authors: Kangchun Wang; Bei Zhao, Yu Liang, Bin Ma
Pages: 21 - 33
Abstract: Colorectal cancer (CRC) is one of the most common tumors in the digestive system, and it is urgent to identify a new biomarker for the diagnosis and treatment of CRC. N6-methyladenosine (m6A) is an abundant mRNA modification and is almost involved in every aspect of physiological processes. In this study, we constructed a novel m6A-related 2-lncRNAs signature that can predict the prognosis of CRC. We obtained m6A-related lncRNAs and identified prognostic lncRNAs through univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis, then constructed a prognostic model based on the risk score, and we also verified the stability of the model. In addition, differential expression analysis between the high- and low-risk subgroups was performed. A total of 1,894 m6A-related lncRNAs were screened from various sources. Using univariate Cox regression analysis and survival analysis, two lncRNAs (AL135999.1 and AL049840.4) were identified (P < 0.05), and the coefficients of lncRNAs were calculated by LASSO. The high-risk group had worse clinical outcomes and overall survival (OS) than the low-risk group, and the risk score can serve as an independent prognostic factor in CRC. In addition, different stages of CRC also showed a different level of risk score. Finally, we found that two lncRNAs were differentially expressed (P < 0.01) in CRC patients, and AL135999.1 may be relevant to m6A modification mediated by methyltransferase-like 3 (METTL3) in CRC. In summary, we constructed a reliable 2-lncRNAs signature based on the risk score, and we identified two m6A-related prognostic lncRNAs, AL135999.1 and AL049840.4. The novel 2-lncRNAs signature plays an essential role in predicting the prognosis of CRC.
Citation: Journal of Cancer
PubDate: 2022
Issue No: Vol. 13, No. 1 (2022)
- Hsa_circ_0074298 promotes pancreatic cancer progression and resistance to
gemcitabine by sponging miR-519 to target SMOC
Authors: Chen Hong; Wang Lishan, Xie Peng, Lei Zhengqing, Yang Yang, Hu Fangfang, Yu Zeqian, Cheng Zhangjun, Zhou Jiahua
Pages: 34 - 50
Abstract: Objective: To investigate the expression of hsa_circ_0074298 (circular RNA) and the molecular mechanism that promotes tumor growth and enhances the chemoresistance of pancreatic cancer.Methods: Real-time reverse transcription-PCR was used to detect hsa_circ_0074298 expression in pancreatic cancer. The intracellular localization of hsa_circ_0074298 was determined by RNA in situ hybridization. The CCK8 method, colony formation assay, Transwell assay, and flow cytometry were used to evaluate the effects of hsa_circ_0074298 on the proliferation, migration, invasion, cell cycle, apoptosis of pancreatic cancer cells. Bioinformatics analysis and dual luciferase assays were employed to detect the association of hsa_circ_0074298 and miR-519d and the binding of miR-519d to the target gene SMOC2. A subcutaneous xenograft model was established to observe the effect of hsa_circ_0074298 in vivo.Results: The hsa_circ_0074298 was mainly localized in the cytoplasm. Hsa_circ_0074298 was highly expressed in pancreatic cancer tissues and cell lines. The expression of hsa_circ_0074298 was significantly correlated with pancreatic cancer tumor size, lymph node metastasis, and pathological grade. hsa_circ_0074298 could sponge miR-519, and miR-519d bound to SMOC2. Downregulation of hsa_circ_0074298 expression significantly inhibited cell proliferation, migration, invasion, colony forming ability and promoted cell cycle arrest, apoptosis and chemo-resistance of pancreatic cancer in vitro and vivo. However, the effects could be reversed by a miR-519d inhibitor or SMOC2 overexpression.Conclusion: By sponging miR-519 and targeting SMOC2, hsa_circ_0074298 promotes the growth and metastasis of pancreatic cancer and increases the resistance of pancreatic cancer cells to gemcitabine.
Citation: Journal of Cancer
PubDate: 2022
Issue No: Vol. 13, No. 1 (2022)
- The Association between Pretreatment anemia and Overall Survival in
Advanced Non-small Cell lung Cancer: A Retrospective Cohort Study Using
Propensity Score Matching
Authors: Yucong Huang; Cuiyun Su, Huiqin Jiang, Feiwen Liu, Qitao Yu, Shaozhang Zhou
Pages: 51 - 61
Abstract: Background: The purpose of this study was to investigate whether pretreatment anemia was an independent risk factor for survival in patients with advanced non-small cell lung cancer (NSCLC) after adjusting for other covariates.Methods: We used propensity score matching (PSM) to minimize the influence of confounding factors and used χ2 (categorical variables), Student's t-test (normal distribution), or Mann-Whitney U test (skewed distribution) to analyze the differences among the Hb groups. Cox regression and Kaplan-Meier analyses were used to assess the association between anemia and survival. P values < 0.05 (two-sided) were considered statistically significant.Results: The average age of the 758 selected participants was 58.2±11 years, and 210 patients (27.7%) had anemia. In the multivariate analysis, anemia was associated with a poor prognosis in the unmatched cohort (Hazards ratio (HR)=1.3, 95% (confidence interval (CI): 1.1-1.6; p= 0.008), and the matched cohort (HR=1.7, 95% CI: 1.3-2.3; p
Citation: Journal of Cancer
PubDate: 2022
Issue No: Vol. 13, No. 1 (2022)
- Ago-RIP Sequencing Identifies New MicroRNA-449a-5p Target Genes Increasing
Sorafenib Efficacy in Hepatocellular Carcinoma
Authors: Thea Reinkens; Amelie Stalke, Nicole Huge, Beate Vajen, Marlies Eilers, Vera Schäffer, Oliver Dittrich-Breiholz, Brigitte Schlegelberger, Thomas Illig, Britta Skawran
Pages: 62 - 75
Abstract: BACKGROUND: Patients with hepatocellular carcinoma (HCC) have very limited treatment options. For the last fourteen years, the multi-tyrosine kinase inhibitor sorafenib has been used as standard-of-care therapeutic agent in advanced HCC. Unfortunately, drug resistance develops in many cases. Therefore, we aimed to find a way to mitigate drug resistance and to improve the sorafenib efficacy in HCC cells. MicroRNAs play a significant role in targeting genes involved in tumor control suggesting microRNA/sorafenib combination therapy as a promising treatment option in advanced HCC.METHODS: MiR-449a-5p target genes were identified by Ago-RIP sequencing and validated by luciferase reporter assays and expression analyses. Target gene expression and survival data were analyzed in public HCC datasets. Tumor-relevant functional effects of miR-449a-5p and its target genes as well as their impact on the effects of sorafenib were analyzed using in vitro assays. An indirect transwell co-culture system was used to survey anti-angiogenic effects of miR-449a-5p.RESULTS: PEA15, PPP1CA and TUFT1 were identified as direct target genes of miR-449a-5p. Overexpression of these genes correlated with a poor outcome of HCC patients. Transfection with miR-449a-5p and repression of miR-449a-5p target genes inhibited cell proliferation and angiogenesis, induced apoptosis and reduced AKT and ERK signaling in HLE and Huh7 cells. Importantly, miR-449a-5p potentiated the efficacy of sorafenib in HCC cells via downregulation of PEA15, PPP1CA and TUFT1.CONCLUSIONS: This study provides detailed insights into the targetome and regulatory network of miR-449a-5p. Our results demonstrate for the first time that targeting PEA15, PPP1CA and TUFT1 via miR-449a overexpression could have significant implications in counteracting sorafenib resistance suggesting miR-449a-5p as a promising candidate for a microRNA/sorafenib combination therapy.
Citation: Journal of Cancer
PubDate: 2022
Issue No: Vol. 13, No. 1 (2022)
