HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV-related hepatocellular carcinoma by targeting estrogen receptor-α
HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV-related hepatocellular carcinoma by targeting estrogen receptor-α
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DOI：
10.3892/or.2014.3647
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发表时间：
2015-02-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Li-Ping
中科院分区：
文献类型：
--
作者：
Chen, Juan-Juan;Tang, Yi-Shu;Zhang, Li-Ping
B型肝炎病毒X蛋白（HBx）在肝细胞癌（HCC）的发生发展中起重要作用。新出现的证据显示异常表达的miR-221与癌症发展之间存在关联;然而，关于其在B型肝炎病毒（HBV）相关HCC中的潜在作用知之甚少。在本研究中，功能研究表明，HBx导致促进细胞增殖和细胞生长活力。与空白对照组相比，转染HBx的细胞中miR-221明显过表达。抑制miR-221显著抑制HCC细胞增殖。Western blot分析显示，雌激素受体α（ER α）在肝癌组织和细胞系中表达下调。生物信息学分析结合验证实验将ER a鉴定为miR-221的直接靶点。目前的研究表明，miR-221通过抑制ER α调节HCC癌细胞增殖，作为肿瘤促进剂发挥作用。此外，我们的数据表明，miR-221有可能作为HBV相关HCC的miRNA治疗靶点。
Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). Emerging evidence has shown the association between aberrantly expressed miR-221 and cancer development; however, little is known concerning its potential role in hepatitis B virus (HBV)-related HCC. In the present study, functional studies demonstrated that HBx leads to the promotion of cell proliferation and cell growth viability. Obviously overexpressed miR-221 was found in HBx-transfected cells compared with the mock counterparts. Suppression of miR-221 significantly inhibited HCC cell proliferation. Western blot analysis indicated that estrogen receptor-alpha (ER alpha) was downregulated in HCC tissues and cell lines. Bioinformatic analysis combined with validation experiments identified ERa as a direct target of miR-221. The present study suggests that miR-221 modulates HCC cancer cell proliferation by suppressing ER alpha, functioning as a tumor promoter. Moreover, our data imply that miR-221 has potential as an miRNA-based therapeutic target for HBV-related HCC.