title: miRNA-135a promotes hepatocellular carcinoma cell migration and invasion by targeting forkhead box O1.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Many microRNAs (miRNAs), small non-coding RNAs, are involved in regulating cancer cell proliferation, metastasis, migration, invasion and apoptosis.
  
  
  METHODS
  We investigated the expression of miR-135a in HCC cell lines and clinical tissues. The effect of miR-135a on migration and invasion of HepG2 and MHCC-97L were examined using wound healing and Transwell assay. We determined the expression of miR-135a, forkhead box O1 (FOXO1), matrix metalloproteinase-2 (MMP-2) and Snail using real-time PCR and western blotting.
  
  
  RESULTS
  We found miR-135a was upregulated in HCC cell lines and tissues. miR-135a overexpression promoted HCC cells migration and invasion, whereas miR-135a inhibition suppressed HCC cells migration and invasion. miR-135a overexpression could upregulate the expression of MMP2, Snail and the phosphorylation of AKT, but decreased FOXO3a phosporylation. Tumor suppressor FOXO1 was the direct target for miR-135a.
  
  
  CONCLUSIONS
  Our results suggested that miR-135a might play an important role in promoting migration and invasion in HCC and presents a novel mechanism of miRNA-mediated direct suppression of FOXO1 in HCC cells.
authors.affiliation: Department of Infectious Diseases, Zengcheng People's Hospital (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, 511300 China.
authors.forename: Yue-Bin
authors.initials: YB
authors.lastname: Zeng
authors.affiliation: Department of Gastroenterology, Zengcheng People's Hospital (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, 511300 China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Liang
authors.affiliation: School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006 China.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Zengcheng People's Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, 511300 China.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Zengcheng People's Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, 511300 China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Zengcheng People's Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, 511300 China.|Department of General Surgery and Clinical Laboratory, Zengcheng People's Hospital (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, 511300 China.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Zeng
keywords: FOXO1; Hepatocellular carcinoma; Migration and invasion; miR-135a