title: microRNA-23b suppresses epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma via targeting Pyk2.
abstract: Numerous microRNAs (miRNAs) have been shown to play important roles in various cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of the miRNAs involved in HCC progress and metastasis still remain unknown. We downloaded the normalized data of microRNA expression profiling of HCC comparing primary tumor with lung metastasis from GEO database (GSE26323), and gain a group of metastasis-related candidate miRNAs. Among the candidate miRNAs, we focused on miR-23b for further study. The association of metastasis-related miR-23b with survival was also explored. Furthermore, the effects of miR-23b on biological role in HCC were demonstrated by MTT proliferation assay, wound healing and migration assay and the EMT related markers was analyzed by Western blot. Potential target genes of miR-23b were predicted using TargetScan and PicTar and confirmed by luciferase activity assay. A rescue experiment was performed to verify whether the function of miR-23b was exerted via regulation of its target. Our results showed that miR-23b expression was significantly decreased in HCC tissues, which was more importantly, positively correlated to the intrahepatic metastasis of HCC. Meanwhile, patients with low miR-23b expression had significantly poorer prognosis. Overexpression of miR-23b could inhibit MHCC97L cell proliferation, migration, invasion and regulate the expression of MMPs and EMT-associated genes. Moreover, Pyk2, one of the crucial regulators of EMT, was identified as a direct target of miR-23b. In addition, the inhibitory effects of miR-23b overexpression on the metastasis could be restored by Pyk2 overexpression. This study revealed that miR-23b was a tumor suppressor which may regulate HCC migration and invasion by targeting Pyk2 via regulation of EMT, implicating a potential prognostic biomarker and therapeutic target for HCC treatment.
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Jinkai
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Long
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai 200438, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China. Electronic address: ehbhyyq@163.com.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Yan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D051418:Focal Adhesion Kinase 2 / Q000037:antagonists & inhibitors*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D016019:Survival Analysis; D014945:Wound Healing / Q000187:drug effects
chemical_list: C531946:23C3 monoclonal antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D051418:Focal Adhesion Kinase 2
keywords: Epithelial-mesenchymal transition; Hepatocellular carcinoma; Metastasis; Pyk2; microRNA-23b