概 要
目 的
研究肝癌细胞缺氧微环境导致 miR-210 表达变化与肿瘤进展、 预后等相关性。
创新点
首次阐明了 miR-210 表达与肝癌预后及缺氧相关基因的关系。
方 法
选取肿瘤基因数据库 (TCGA) 中 424 位肝癌患者的 miR-210 表达水平、 临床病理参数及缺氧相关基因 (HIF1α、 HIF3α、 PTPN1 和 BNIP3) 表达量, 研究 miR-210 与肝癌预后及缺氧基因之间的相关性。
结 论
miR-210 的表达与肝细胞癌进展分期呈正相关, 它的高表达预示更低的无瘤生存率。 因此, 推测 miR-210 可能与肿瘤细胞缺氧相关性死亡有关。
This is a preview of subscription content, log in via an institution to check access.
References
Airley RE, Mobasheri A, 2007. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy, 53(4):233–256. https://doi.org/10.1159/000104457
Bavelloni A, Ramazzotti G, Poli A, et al., 2017. MiRNA-210: a current overview. Anticancer Res, 37(12):6511–6521. https://doi.org/10.21873/anticanres.12107
Brooks DL, Schwab LP, Krutilina R, et al., 2016. ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models. Mol Cancer, 15:26. https://doi.org/10.1186/sl2943-016-0510-x
Heddleston JM, Li Z, Lathia ID, et al., 2010. Hypoxia inducible factors in cancer stem cells. Br J Cancer, 102(5): 789–795. https://doi.org/10.1038/sj.bjc.6605551
Huang X, Le QT, Giaccia AJ, 2010. MiR-210-micromanager of the hypoxia pathway. Trends Mol Med, 16(5):230–237. https://doi.org/10.1016/j.molmed.2010.03.004
Ivan M, Huang X, 2014. MiR-210: fine-tuning the hypoxic response. In: Koumenis C, Hammond E, Giaccia A (Eds.), Tumor Microenvironment and Cellular Stress: Signaling, Metabolism, Imaging, and Therapeutic Targets. Springer, New York, p.205–227. https://doi.org/10.1007/978-l-4614-5915-6_10
Jemal A, Bray F, Center MM, et al, 2011. Global cancer statistics. CA Cancer J Clin, 61(2):69–90. https://doi.org/10.3322/caac.20107
Kai AKL, Chan LK, Lo RCL, et al., 2016. Down-regulation of TIMP2 by HTF-1α/miR-210/HIF-3α regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma. Hepatology, 64(2):473–487. https://doi.org/10.1002/hep.28577
Liu LL, Li DH, He YL, et al, 2017. miR-210 protects renal cell against hypoxia-induced apoptosis by targeting LHF-1 alpha. Mol Med, 23:258–271. https://doi.org/10.2119/molmed.2017.00013
Pugh CW, Ratcliffe PJ, 2003. Regulation of angiogenesis by hypoxia: role of the HTF system. Nat Med, 9(6):677–684. https://doi.org/10.1038/nm0603-677
Semela D, Dufour JF, 2004. Angiogenesis and hepatocellular carcinoma. J Hepatol, 41(5):864–880. https://doi.org/10.1016/jjhep.2004.09.006
Siegel RL, Miller KD, Jemal A, 2018. Cancer statistics, 2018. CA Cancer J Clin, 68(1): 7–30. https://doi.org/10.3322/caac.21442
Silakit R, Kitirat Y, Thongchot S, et al, 2018. Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcita-bine resistance in cholangiocarcinoma cells. PLoS ONE, 13(6):e0199827. https://doi.org/10.1371/journal.pone.0199827
Wan LL, Zhang DQ, Zhang JN, et al, 2017. Anti-hepatocarcinoma activity of TT-1, an analog of melittin, combined with interferon-a via promoting the interaction of NKG2D and MICA. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(6):522–531. https://doi.org/10.1631/jzus.B1600369
ai]Wang LY, Zheng SS, 2018. Advances in predicting the prognosis of hepatocellular carcinoma recipients after liver transplantation. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(7):497–504. https://doi.org/10.1631/jzus.B1700156
Wang ZD, Qu FY, Chen YY, et al., 2017. Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(1):27–36. https://doi.org/10.1631/jzus.B1600205
Yang Y, Zhang J, Xia T, et al., 2016. MicroRNA-210 promotes cancer angiogenesis by targeting fibroblast growth factor receptor-like 1 in hepatocellular carcinoma. Oncol Rep, 36(5):2553–2562. https://doi.org/10.3892/or.2016.5129
Ying Q, Liang LH, Guo WJ, et al., 2011. Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology, 54(6):2064–2075. https://doi.org/10.1002/hep.24614
Author information
Authors and Affiliations
Contributions
Yi DAI performed data analysis, and wrote and edited the manuscript. Ji-liang SHEN, Xue-yong ZHENG, and Tian-yu LIN collected the data. Hai-tao YU contributed to the study design, data analysis, and editing of the manuscript. All authors have read and approved the final manuscript and had full access to all the data in the study. All authors take responsibility for the integrity and security of the data.
Corresponding author
Ethics declarations
Yi DAI, Ji-liang SHEN, Xue-yong ZHENG, Tian-yu LIN, and Hai-tao YU declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Project supported by the Education Department of Zhejiang Province (No. G201432123) and the Public Welfare Technology Application Research Plan Project of Zhejiang Science and Technology Department (No. LGC19H200005), China
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Dai, Y., Shen, Jl., Zheng, Xy. et al. Integrated analysis of hypoxia-induced miR-210 signature as a potential prognostic biomarker of hepatocellular carcinoma: a study based on The Cancer Genome Atlas. J. Zhejiang Univ. Sci. B 20, 928–932 (2019). https://doi.org/10.1631/jzus.B1900343
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B1900343