caa a22 4500 60623425X CHVBK 20210128101236.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2234-9 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2234-9 MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4) [Elektronische Daten] [Jing Xue, Li-Zhang Chen, Zhan-Zhan Li, Ying-yun Hu, Shi-peng Yan, Li-Ya Liu] 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. Springer Science+Business Media New York, 2014 MicroRNA-433 nationallicence Cell proliferation nationallicence PAK4 nationallicence Hepatocellular carcinoma nationallicence HepG2 nationallicence Xue Jing Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut Chen Li-Zhang Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut Li Zhan-Zhan Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut Hu Ying-yun Department of Medical record, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410006, Changsha, China aut Yan Shi-peng Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut Liu Li-Ya Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 77-86 0300-8177 399:1-2<77 2015 399 11010 https://doi.org/10.1007/s11010-014-2234-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2234-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Xue Jing Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut NATIONALLICENCE 700 1- Chen Li-Zhang Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut NATIONALLICENCE 700 1- Li Zhan-Zhan Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut NATIONALLICENCE 700 1- Hu Ying-yun Department of Medical record, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410006, Changsha, China aut NATIONALLICENCE 700 1- Yan Shi-peng Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut NATIONALLICENCE 700 1- Liu Li-Ya Department of Epidemiology, Public Health School of Central South University, 410078, Changsha, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 77-86 0300-8177 399:1-2<77 2015 399 11010