inhibitshepatocellularcarcinomacellproliferation,invasion.docx

MiRNA-144 inhibits hepatocellular carcinoma cell proliferation, invasion and migration through targeting ZFXRunning title: miR-144 targeted ZFX in hepatocellular carcinomaHongbinBao*, Xinguo Li, Hengli Li, Hongli Xing, Binghui Xu, Xianfeng Zhang, Zhaoming LiuDepartment of hepatobiliary surgery, Harrison International Peace Hospital, Hengshui City, Hebei province, China*Corresponding author: HongbinBao, Department of hepatobiliary surgery, Harrison International Peace Hospital, No.180 East People’s Road, 053000, Hengshui, ChinaTel: +86-0318-2181234Email: hongbinB_112@163.comAbstractMicroRNA 144 (miR-144), a small non-coding RNA, is frequently dysregulated in human several tumor progression, but its role and the underlying mechanisms in hepatocellular carcinoma (HCC) is poorly investigated. In the present study, the expression of miR-144 was firstly analyzed in datasets derived from GSE21362 and TCGA, and then detected in HCC tissues and cell lines by quantitative RT-PCR (qRT-PCR) analysis. MiR-144 was shown to be significantly down-regulated in HCC tissues and cell lines. Subsequently, overexpression of miR-144 was transfected into HCC cell lines to investigate its biological function, including MTT, colony formation, transwell assays. Gain of function assay revealed miR-144 remarkably inhibited cell proliferation, migration and invasion. In addition, bioinformatical analysis and luciferase reporter assay identified ZFX as a novel target of miR-144 in HCC cells, as confirmed by qRT-PCR and Western blot. Furthermore, ZFX was found to be significantly upregulated using Oncomine database analysis. Loss of function assay further indicated knockdown of ZFX had similar effects of miR-144-mediated HCC cell proliferation and invasion. Therefore, miR-144 has been demonstrated to act as a tumor suppressor in HCC cell growth and motility by directly targeting ZFX, which implicates its potential applications in the development of HCC treatment.Key words: miR-144, Hepatocellular