王涛, 李东, 彭晶晶, 刘煜, 孙非凡, 王丹, 程朋, 苏晓妹, 张伶, 高辉, 原薇薇, 李华, 张涛. miR-375调控PDGFC基因表达抑制肝癌血管生成[J]. 中国肿瘤临床, 2017, 44(20): 1007-1013. DOI: 10.3969/j.issn.1000-8179.2017.20.689
引用本文: 王涛, 李东, 彭晶晶, 刘煜, 孙非凡, 王丹, 程朋, 苏晓妹, 张伶, 高辉, 原薇薇, 李华, 张涛. miR-375调控PDGFC基因表达抑制肝癌血管生成[J]. 中国肿瘤临床, 2017, 44(20): 1007-1013. DOI: 10.3969/j.issn.1000-8179.2017.20.689
WANG Tao, LI Dong, PENG Jingjing, LIU Yu, SUN Feifan, WANG Dan, CHENG Peng, SU Xiaomei, ZHANG Lin, GAO Hui, YUAN Weiwei, LI Hua, ZHANG Tao. MiR-375 suppresses angiogenesis of hepatocellular carcinoma by targeting platelet-derived growth factor-C[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2017, 44(20): 1007-1013. DOI: 10.3969/j.issn.1000-8179.2017.20.689
Citation: WANG Tao, LI Dong, PENG Jingjing, LIU Yu, SUN Feifan, WANG Dan, CHENG Peng, SU Xiaomei, ZHANG Lin, GAO Hui, YUAN Weiwei, LI Hua, ZHANG Tao. MiR-375 suppresses angiogenesis of hepatocellular carcinoma by targeting platelet-derived growth factor-C[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2017, 44(20): 1007-1013. DOI: 10.3969/j.issn.1000-8179.2017.20.689

miR-375调控PDGFC基因表达抑制肝癌血管生成

MiR-375 suppresses angiogenesis of hepatocellular carcinoma by targeting platelet-derived growth factor-C

  • 摘要:
      目的  miR-375已被证明能够抑制肝癌细胞增殖、迁移和侵袭,促进肝癌细胞凋亡,本研究旨在探索miR-375对肝癌新生血管生成的影响及其分子机制。
      方法  利用血管生成相关的功能实验探索miR-375对肝癌新生血管生成的影响;使用生物信息学方法预测miR-375潜在的与血管生成相关的功能靶基因;在肝癌细胞系中过表达和下调表达miR-375,验证miR-375对靶基因的调控作用,并利用双荧光素酶报告实验明确其分子机制;靶基因功能挽救实验明确miR-375通过调控靶基因的表达发挥抑制肝癌新生血管生成的作用。
      结果  miR-375能够抑制肝癌新生血管生成;血小板源性生长因子C(PDGFC)是miR-375的潜在功能靶基因;miR-375能够直接作用于PDGFC基因mRNA 3'-非编码端(3'-UTR)而抑制PDGFC基因表达;miR-375能够通过抑制PDGFC基因表达抑制肝癌新生血管生成。
      结论  miR-375能够调控PDGFC基因表达抑制肝癌新生血管生成。

     

    Abstract:
      Objective  Abnormal angiogenesis is an important hallmark of HCC. Ectopic miR-375 overexpression led to repression of proliferation, migration, invasion, and colony formation, and it induced apoptosis in hepatoma cells as well. In this study, we explored the effect of miR-375 on HCC angiogenesis.
      Methods  We evaluated the antiangiogenic effects of miR-375 using human umbilical vein endothelial cells, tube formation assays, rat aortic ring sprouting assays, and chicken chorioallantoic membrane assays. Bioinformatics software was used to predict the downstream target gene of miR-375. MiR-375 regulation to target genes was explored by overexpression and knockdown of miR-375 in hepatoma cells. Luciferase assay was performed to confirm its molecular mechanism. Rescue assay of target gene was further used to prove that miR-375 inhibited HCC angiogenesis by directly regulating its target gene.
      Results  MiR-375 inhibited HCC angiogenesis. Platelet-derived growth factor-C (PDGFC) was a potential target gene of miR-375. MiR-375 inhibited PDGFC expression in hepatoma cells by targeting its 3′-UTR. MiR-375 exerted its antiangiogenic effect partially by PDGFC inhibition.
      Conclusion  MiR-375 repressed tumor angiogenesis by targeting PDGFC in HCC.

     

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