title: miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and the third leading cause of cancer-related deaths worldwide. Tumour metastasis is one of the major causes of high mortality. microRNAshave been implicated in HCC metastasis. In this study, we found that miR-625 was frequently downregulated in HCC samples. A decrease in miR-625 was significantly correlated with lymph node anddistance metastasis (P=0.013), the presence of portal venous invasion (P=0.036), tumor-node-metastasis (TNM) stage (P=0.027) and unfavourable overall survival (P=0.003). Compared with primary tumours, miR-625 expression was markedly reduced in portal venous metastatic tumours. Re-expression of miR-625 in HCC cells was remarkably effective in suppressing cell migration andinvasiveness in vitro and in vivo. Mechanistically, miR-625 was confirmed to downregulate IGF2 mRNA-binding protein 1(IGF2BP1) directly, the expression of which was inversely correlated with the level of miR-625 in HCC cell lines and tissues. High expression of IGF2BP1 was frequently found in HCC samples, and associated with poor prognosis. Knockdown of endogenous IGF2BP1 by siRNA exhibited similar effects as the overexpression of miR-625, whereas overexpression of IGF2BP1 (without the 3'-UTR) abrogated miR-625-mediated metastasis inhibition. Interference of the PTEN/HSP27 pathway contributed to miR-625-mediated metastasis inhibition. Taken together, our data suggest that miR-625 might function as an antimetastatic miRNA to have an important role in HCC progression by modulating the IGF2BP1/PTEN pathway. The newly identified miR-625/IGF2BP1 axis represents a new potential therapeutic target for HCC treatment.
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China [3] Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: C Z
authors.initials: CZ
authors.lastname: Zhang
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: S-X
authors.initials: SX
authors.lastname: Lu
authors.affiliation: Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: G G
authors.initials: GG
authors.lastname: Chen
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: L-Z
authors.initials: LZ
authors.lastname: Li
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: L-L
authors.initials: LL
authors.lastname: Liu
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Yi
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: J-M
authors.initials: JM
authors.lastname: Wen
authors.affiliation: 1] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China [2] Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: J-P
authors.initials: JP
authors.lastname: Yun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016601:RNA-Binding Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: C406144:IGF2BP1 protein, human; C575476:MIRN625 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins