title: MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4).
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.
authors.affiliation: Department of Epidemiology, Public Health School of Central South University, Changsha, 410078, China, 406912119@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Li-Zhang
authors.initials: LZ
authors.lastname: Chen
authors.forename: Zhan-Zhan
authors.initials: ZZ
authors.lastname: Li
authors.forename: Ying-yun
authors.initials: YY
authors.lastname: Hu
authors.forename: Shi-peng
authors.initials: SP
authors.lastname: Yan
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C548883:MIRN433 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; C116367:PAK4 protein, human; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases