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MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4)

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. P21-activated kinase 4 (PAK4) has been identified as an oncogenic protein in a variety of cancers. However, the contribution and regulation of PAK4 in HCC remain poorly understood. In the present study, we found that inhibition of PAK4 expression by specific shRNA significantly attenuated HCC cell proliferation. Moreover, we show that microRNA-433 (miRNA-433) could directly target PAK4 through the miRNA-433 binding sequence at the 3′-UTR of PAK4 mRNA, and inhibit PAK4 protein expression. We further show that miRNA-433 expression was downregulated in HCC tissues and cell culture as well, which inversely correlated with PAK4 expression levels. Overexpression of miRNA-433 significantly suppressed the proliferation of HepG2 cells, while this effect was partially rescued by forced expression of PAK4 through restoring PI3K/AKT signaling in HepG2 cells. These findings will shed light on the roles and mechanisms of miRNA-433 in regulating HCC proliferation, and may benefit future development of therapeutics targeting miRNA-433 and PAK4 in HCC.

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Acknowledgments

This work was supported in part by the The China Scholarship Council (No. 201306370138) and the Science & Technology Department of Hunan Province (2012FJ4133).

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology, Public Health School of Central South University, Changsha, 410078, China

    Jing Xue, Li-Zhang Chen, Zhan-Zhan Li, Shi-peng Yan & Li-Ya Liu

  2. Department of Medical record, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410006, China

    Ying-yun Hu

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  1. Jing Xue
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Correspondence to Li-Zhang Chen.

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Xue, J., Chen, LZ., Li, ZZ. et al. MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4). Mol Cell Biochem 399, 77–86 (2015). https://doi.org/10.1007/s11010-014-2234-9

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