MicroRNA-433 Inhibits Cell Proliferation in Hepatocellular Carcinoma by Targeting P21 Activated Kinase (PAK4)

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2014 Nov 21

PMID 25410752

Citations 14

Authors

Jing Xue

Li-Zhang Chen

Zhan-Zhan Li

Ying-Yun Hu

Shi-Peng Yan

Li-Ya Liu

Affiliations

Soon will be listed here.

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.

Citing Articles

P-21 Activated Kinases in Liver Disorders.

Qiu X, Xu H, Wang K, Gao F, Xu X, He H Cancers (Basel). 2023; 15(2).

PMID: 36672500 PMC: 9857091. DOI: 10.3390/cancers15020551.

The Inhibitory Mechanism of 7-Pyrrolo[2,3-d]pyrimidine Derivatives as Inhibitors of P21-Activated Kinase 4 through Molecular Dynamics Simulation.

Du J, Wang S, Zhang X, Liu C, Zhang Y, Zhang H Molecules. 2023; 28(1).

PMID: 36615619 PMC: 9823812. DOI: 10.3390/molecules28010413.

p21-Activated kinases as promising therapeutic targets in hematological malignancies.

Wu A, Jiang X Leukemia. 2021; 36(2):315-326.

PMID: 34697424 DOI: 10.1038/s41375-021-01451-7.

PAK4 suppresses motor neuron degeneration in hSOD1 -linked amyotrophic lateral sclerosis cell and rat models.

Cong C, Liang W, Zhang C, Wang Y, Yang Y, Wang X Cell Prolif. 2021; 54(4):e13003.

PMID: 33615605 PMC: 8016643. DOI: 10.1111/cpr.13003.

MiR-193-3p attenuates the vascular remodeling in pulmonary arterial hypertension by targeting PAK4.

Wu Z, Geng J, Qi Y, Li J, Bai Y, Guo Z Pulm Circ. 2020; 10(4):2045894020974919.

PMID: 33354317 PMC: 7734527. DOI: 10.1177/2045894020974919.

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