title: MiR-218 suppresses the metastasis and EMT of HCC cells via targeting SERBP1.
abstract: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. Although many efforts for treating HCC have been made, the survival rate remains unsatisfied. Accumulating evidence indicates that microRNA-218 (miR-218) functions as a tumor suppressor and involves in many biological processes such as tumor initiation, development, and metastasis in certain types of human cancers. However, the potential function and underlying molecular mechanism of miR-218 in HCC still remains to be elucidated. Since HCC is a genetic disease, exploring the mechanisms of the pathogeny and integration are essential for the discovery of novel treatment targets for HCC. Therefore, the aim of the present study was to investigate the abnormal expression level of miR-218 in clinical HCC tissues and HCC cells, and to evaluate its function and underlying mechanisms in HCC. Our results revealed that miR-218 expression was significantly downregulated in HCC tissues and cell lines. Gain-of-function and loss-of-function assays indicated that forced expression of miR-218 in HCC cells inhibited cell migration/invasion and reversed epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET), while deletion of miR-218 promoted cell migration/invasion and contributed to the EMT phenotype formation. Bioinformatics analysis and luciferase reporter assay confirmed that serpine mRNA binding protein 1 (SERBP1) was a target gene of miR-218 and rescue assay further confirmed that SERBP1 involved in the function of miR-218 in HCC. All these results suggested that miR-218/SERBP1 signal pathway could inhibit the malignant phenotype formation and that targeting this pathway may be a potential novel way for HCC therapeutics.
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wei
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000556:secondary*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C428129:SERBP1 protein, human
keywords: EMT; HCC; SERBP1; metastasis; miR-218