MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/β-catenin pathway.
MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/β-catenin pathway.
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MiR-148b 通过靶向 WNT1/β-catenin 通路抑制肝细胞癌细胞增殖和侵袭
DOI：
10.1038/srep08087
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发表时间：
2015-01-28
影响因子：
4.6
通讯作者：
Zhao G
中科院分区：
文献类型：
--
作者：
Zhang JG;Shi Y;Hong DF;Song M;Huang D;Wang CY;Zhao G
越来越多的证据表明microRNA在调节肿瘤进展中起着重要作用。然而，miR-148 b在肝细胞癌（HCC）中的作用仍然很大程度上未知。在这项研究中，我们的数据显示，miR-148 b在40对人HCC组织中显著下调。miR-148 b表达下调与肝癌的肿瘤体积、数量、转移和预后密切相关。miR-148 b过表达可抑制肝癌细胞HepG 2的增殖和致瘤性。miR-148 b通过激活caspase- 3和caspase-9诱导细胞凋亡，通过调节cyclinD 1和p21诱导S期阻滞，并抑制细胞侵袭。来自双荧光素酶报告基因测定的数据显示，WNT 1是miR-148 b的直接靶点，并且在HCC组织中过表达的WNT 1与miR-148 b水平呈负相关。WNT 1基因的沉默抑制了肝癌细胞的生长，并诱导细胞凋亡和抑制侵袭，这与miR-148 b过表达的作用一致。miR-148 b下调WNT 1、β-catenin和C-myc的表达，上调E-cadherin的表达。结论：miR-148 b在肝癌中的表达下调，可能通过调节WNT 1/β-catenin信号通路发挥抑癌作用。这些发现表明miR-148 b可能作为HCC的新治疗靶点。
Accumulating evidences indicate that microRNAs play a vital role in regulating tumor progression. However, the roles of miR-148b in hepatocellular carcinoma (HCC) are still largely unknown. In this study, our data showed that miR-148b was significantly downregulated in 40 pairs of human HCC tissues. Further, the deregulated miR-148b was significantly correlated with larger tumor size, more tumor number, metastasis and worse prognosis in HCC. Overexpression of miR-148b inhibited HCC HepG2 cells proliferation and tumorigenicity. Further, miR-148b induced cells apoptosis by activating caspase- 3 and caspase-9, and induced S phase arrest by regulating cyclinD1 and p21, and also inhibited cell invasion. Data from the dual-luciferase reporter gene assay showed that WNT1 was a direct target of miR-148b, and overexpressed WNT1 inversely correlated with miR-148b levels in HCC tissues. Silencing of WNT1 inhibited the growth of HCC cells, and also induced cells apoptosis and inhibited invasion, which is consistent with the effects of miR-148b overexpression. MiR-148b downregulated expression of WNT1, β-catenin and C-myc, while upregulated E-cadherin expression. We conclude that the frequently downregulated miR-148b can regulate WNT1/β-catenin signalling pathway and function as a tumor suppressor in HCC. These findings suggest that miR-148b may serve as a novel therapeutic target for HCC.
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