miR-23c suppresses tumor growth of human hepatocellular carcinoma by attenuating ERBB2IP
miR-23c suppresses tumor growth of human hepatocellular carcinoma by attenuating ERBB2IP
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miR-23c 通过减弱 ERBB2IP 抑制人肝细胞癌的肿瘤生长。
DOI：
10.1016/j.biopha.2018.07.155
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发表时间：
2018-11-01
影响因子：
7.5
通讯作者：
Liu, Qingguang
中科院分区：
文献类型：
--
作者：
Zhang, Lei;Wang, Yufeng;Liu, Qingguang
MicroRNAs(MiRNAs)调控多种发育和生理过程，在包括肝细胞癌在内的人类肿瘤的发生和发展中发挥重要作用。MiR-23c是近年来出现的一种与肿瘤相关的miRNA，但其在肝细胞癌中的表达状况和功能尚不清楚。在此，我们基于TCGA数据发现miR-23c的低表达与肝细胞癌的发生有关。QRT-PCR分析显示miR-23c在肝细胞癌组织和细胞系中表达下调。临床分析表明，miR-23c低表达与肝癌患者肿瘤体积大、分级高、分期高、生存期差有关。我们的体外实验发现，miR-23c的过表达抑制了细胞的增殖并诱导了肝癌细胞的凋亡。MiR-23c基因敲除可导致肝癌细胞生长停滞和细胞凋亡。此外，在体内，miR-23c过表达抑制了肿瘤的生长。在机制上，ERBB2相互作用蛋白(ERBB2IP)被认为是肝癌细胞中miR-23c的直接靶点。MIR-23c抑制肝癌细胞中ERBB2IP的表达，并与肝细胞癌组织中ERBB2IP的表达呈负相关。值得注意的是，ERBB2IP沉默抑制了肝癌细胞的增殖并诱导了细胞凋亡。ERBB2IP修复逆转了miR-23c对肝癌细胞生长的抑制作用。综上所述，我们的观察表明miR-23c通过抑制ERBB2IP而抑制细胞增殖，促进细胞凋亡。靶向miR-23c可能为肝癌的治疗开辟一条新的途径。
MicroRNAs (miRNAs) regulate a variety of development and physiologic processes, and play prominent roles in the initiation and progression of human cancers including hepatocellular carcinoma (HCC). MiR-23c is recently emerging as a cancer-associated miRNA, while its expression status and functional role in HCC are unrevealed yet. Here, we found that miR-23c underexpression was associated with the tumorigenesis of HCC based on TCGA data. qRT-PCR analysis revealed that miR-23c expression was reduced in HCC tissues and cell lines. Clinical analysis indicated that low miR-23c expression was correlated with large tumor size, high tumor grade, advanced tumor stage and poor survival of HCC patients. Our in vitro experiments found that overexpression of miR-23c inhibited cell proliferation and induced apoptosis of HCC cells. While miR-23c knockdown led to HCC cell growth arrest and apoptosis. Additionally, miR-23c overexpression repressed tumor growth of HCC in vivo. Mechanistically, erbb2 interacting protein (ERBB2IP) was identified as a direct target of miR-23c in HCC cells. miR-23c suppressed ERBB2IP expression in HCC cells and inversely correlated with ERBB2IP mRNA expression in HCC tissues. Notably, ERBB2IP silencing restrained HCC cell proliferation and induced apoptosis. ERBB2IP restoration reversed the inhibitory effects of miR-23c on HCC cell growth. In conclusion, our observations suggested that miR-23c inhibited cell proliferation and accelerated apoptosis by attenuating ERBB2IP. Targeting miR-23c might open a new avenue for HCC treatment.