Journal Article

MicroRNA-423 promotes cell growth and regulates G<sub>1</sub>/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma

Jun Lin, Shenglin Huang, Shunquan Wu, Jie Ding, Yingjun Zhao, Linhui Liang, Qi Tian, Ruopeng Zha, Rong Zhan and Xianghuo He

in Carcinogenesis

Volume 32, issue 11, pages 1641-1647
Published in print November 2011 | ISSN: 0143-3334
Published online September 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr199
MicroRNA-423 promotes cell growth and regulates G1/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma

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MicroRNAs (miRNAs) are small non-coding RNA molecules that are often located in genomic breakpoint regions and can act as oncogenes or tumor suppressor genes in human cancer. Our previous study showed that microRNA-423 (miR-423), which localized to the frequently amplified region of chromosome 17q11, was upregulated in hepatocellular carcinoma (HCC). However, the potential functions and exact mechanistic roles of miR-423 in hepatic carcinogenesis remain unknown. Here, we demonstrated that miR-423 significantly promotes cell growth and cell cycle progression at the G1/S transition in HCC cells. In particular, we found that miR-423-3p contributes to these effects, whereas miR-423-5p does not. Further studies revealed that p21Cip1/Waf1 is a downstream target of miR-423 in HCC cells, as miR-423 bound directly to its 3′ untranslated region and reduced both the messenger RNA and protein levels of p21Cip1/Waf1. Moreover, enforced expression of p21Cip1/Waf1 abrogated miR-423-induced effects on HCC cell proliferation and cell cycle progression. These findings indicate that miR-423 exerts growth-promoting effects in hepatic carcinogenesis through the suppression of tumor suppressor p21Cip1/Waf1 expression. The results of this study define miR-423 as a new oncogenic miRNA in HCC.

Journal Article.  3612 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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