Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by targeting p21 expression.
Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by targeting p21 expression.
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肝细胞癌中 miR-95-3p 的上调通过靶向 p21 表达促进肿瘤发生
DOI:
10.1038/srep34034
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发表时间:
2016-10-04
影响因子:
4.6
通讯作者:
Wang QK
中科院分区:
文献类型:
--
作者:
Ye J;Yao Y;Song Q;Li S;Hu Z;Yu Y;Hu C;Da X;Li H;Chen Q;Wang QK
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers. To elucidate new regulatory mechanisms for heptocarcinogenesis, we investigated the regulation of p21, a cyclin-dependent kinase (CDK) inhibitor encoded by CDKN1A, in HCC. The expression level of p21 is decreased with the progression of HCC. Luciferase assays with a luciferase-p21-3′ UTR reporter and its serial deletions identified a 15-bp repressor element at the 3′-UTR of CDKN1A, which contains a binding site for miR-95-3p. Mutation of the binding site eliminated the regulatory effect of miR-95-3p on p21 expression. Posttranscriptional regulation of p21 expression by miR-95-3p is mainly on the protein level (suppression of translation). Overexpression of miR-95-3p in two different HCC cell lines, HepG2 and SMMC7721, significantly promoted cell proliferation, cell cycle progression and cell migration, whereas a miR-95-3p specific inhibitor decreased cell proliferation, cell cycle progression and cell migration. The effects of miR-95-3p on cellular functions were rescued by overexpression of p21. Overexpression of miR-95-3p promoted cell proliferation and tumor growth in HCC xenograft mouse models. Expression of miR-95-3p was significantly higher in HCC samples than in adjacent non-cancerous samples. These results demonstrate that miR-95-3p is a potential new marker for HCC and regulates hepatocarcinogenesis by directly targeting CDKN1A/p21 expression.
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影响因子:
14.9
作者:
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者:
Guegler KJ
影响因子:
--
作者:
Prasad R;Katiyar SK
通讯作者:
Katiyar SK
影响因子:
4.8
作者:
Li, Y;Dowbenko, D;Lasky, LA
通讯作者:
Lasky, LA
影响因子:
--
作者:
Hwang SJ;Lee HW;Kim HR;Song HJ;Lee DH;Lee H;Shin CH;Joung JG;Kim DH;Joo KM;Kim HH
通讯作者:
Kim HH
影响因子:
5.3
作者:
Lee, Ji Young;Yu, Su Jin;Sohn, Jeongwon
通讯作者:
Sohn, Jeongwon