MiR-216b is involved in pathogenesis and progression of hepatocellular carcinoma through HBx-miR-216b-IGF2BP2 signaling pathway.
MiR-216b is involved in pathogenesis and progression of hepatocellular carcinoma through HBx-miR-216b-IGF2BP2 signaling pathway.
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miR-216b通过HBx-miR-216b-IGF2BP2信号通路参与肝细胞癌的发病和进展
DOI：
10.1038/cddis.2015.46
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发表时间：
2015-03-05
影响因子：
9
通讯作者：
Chen XP
中科院分区：
文献类型：
--
作者：
Liu FY;Zhou SJ;Deng YL;Zhang ZY;Zhang EL;Wu ZB;Huang ZY;Chen XP
本研究旨在探讨miRNA-216 b在家族性肝细胞癌（familial hepatocellular carcinoma，HCC）中的表达状况及其与HCC发生、发展的关系。采用基因芯片技术检测有肝癌家族史的肝癌患者和无肝癌家族史的健康志愿者外周血中miRNAs的表达谱。采用实时荧光定量PCR检测150例HCC患者配对组织中的表达情况，选择miR-216 b，其在HCC患者中的表达值明显低于健康志愿者。接下来，评估miR-216 b表达和HCC的临床病理特征。通过在体外和体内调控SMMC-7721和HepG 2中miR-216 b的表达来研究miR-216 b表达对肿瘤细胞的影响。最后，我们探索了miR-216 b的mRNA靶点。在150例HCC中，37例（75%）肿瘤与其邻近肝组织相比显示miR-216 b表达降低。miR-216 b的表达与肿瘤体积（P= 0.044）、HBV感染（P= 0.026）、HBV DNA定量（P= 0.001）和血管浸润（P= 0.032）显著相关。miR-216 b低表达组和高表达组肝切除术后5年无病生存率和总生存率分别为62%和54%、25%和20%。miR-216 b过表达抑制细胞增殖、迁移和侵袭，而miR-216 b抑制则相反。B型肝炎病毒x蛋白（HBx）的表达与miR-216 B的下调密切相关。此外，miR-216 B b下调胰岛素样生长因子2 mRNA结合蛋白2（IGF 2BP 2）的表达，并通过抑制蛋白激酶B和IGF 2下游的细胞外信号调节激酶信号传导发挥其肿瘤抑制功能。MiR-216 b通过调节IGF 2BP 2来抑制肝癌细胞的增殖、迁移和侵袭，并且它受到HBx的调节。
This study aims to investigate the expression status of miRNA-216b in familial hepatocellular carcinoma (HCC) and the correlation between miRNA-216b expression and pathogenesis, as well as the progression of HCC. The expression profile of miRNAs in plasma of peripheral blood between HCC patients with HCC family history and healthy volunteers without HCC family history was determined by microarray. Using real-time quantitative PCR to detect the expression in paired tissues from 150 patients with HCC, miR-216b was selected as its expression value in HCC patients was significantly lower compared with healthy volunteers. Next, miR-216b expression and the clinicopathological features of HCC were evaluated. The effect of miR-216b expression on tumor cells was investigated by regulating miR-216b expression in SMMC-7721 and HepG2 in vitro and in vivo. Finally, we explored mRNA targets of miR-216b. In 150 HCC, 37 (75%) tumors showed reduced miR-216b expression comparing with their adjacent liver tissues. The decreased expression of miR-216b was significantly correlated with tumor volume (P= 0.044), HBV infection (P= 0.026), HBV DNA quantitative (P= 0.001) and vascular invasion (P= 0.032). The 5-year disease-free survival and overall rates after liver resection in low expression and high expression groups of miR-216b are 62% and 54%, 25% and 20%, respectively. MiR-216b overexpression inhibited cell proliferation, migration and invasion, and miR-216b inhibition did the opposite. The expression of hepatitis B virus x protein (HBx) has tight correlation with downregulation of miR-216b. Furthermore, miR-216b downregulated the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and exerted its tumor-suppressor function through inhibition of protein kinase B and extracellular signal-regulated kinase signaling downstream of IGF2. MiR-216b inhibits cell proliferation, migration and invasion of HCC by regulating IGF2BP2 and it is regulated by HBx.
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作者：
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通讯作者：
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影响因子：
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作者：
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