title: microRNA-622 acts as a tumor suppressor in hepatocellular carcinoma.
abstract: microRNAs (miRNAs) are important regulators of tumor development and progression. In this study, we aimed to explore the expression and role of miR-622 in hepatocellular carcinoma (HCC). We found that miR-622 was significantly downregulated in human HCC specimens compared to adjacent noncancerous liver tissues. miR-622 downregulation was significantly associated with aggressive parameters and poor prognosis in HCC. Enforced expression of miR-622 significantly decreased the proliferation and colony formation and induced apoptosis of HCC cells. In vivo studies demonstrated that miR-622 overexpression retarded the growth of HCC xenograft tumors. Bioinformatic analysis and luciferase reporter assays revealed that miR-622 directly targeted the 3'-untranslated region (UTR) of mitogen-activated protein 4 kinase 4 (MAP4K4) mRNA. Ectopic expression of miR-622 led to a significant reduction of MAP4K4 expression in HCC cells and xenograft tumors. Overexpression of MAP4K4 partially restored cell proliferation and colony formation and reversed the induction of apoptosis in miR-622-overexpressing HCC cells. Inhibition of JNK and NF-κB signaling phenocopied the anticancer effects of miR-622 on HCC cells. Taken together, miR-622 acts as a tumor suppressor in HCC and restoration of miR-622 may provide therapeutic benefits in the treatment of HCC.
authors.affiliation: a Department of Interventional Oncology ; Renji Hospital; School of Medicine; Shanghai Jiao Tong University ; Shanghai , China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Song
authors.affiliation: b Department of Pathology ; Yueyang Hospital; Shanghai University of Traditional Chinese Medicine ; Shanghai , China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Feng
authors.affiliation: a Department of Interventional Oncology ; Renji Hospital; School of Medicine; Shanghai Jiao Tong University ; Shanghai , China.
authors.forename: Shao-Juan
authors.initials: SJ
authors.lastname: Gong
authors.affiliation: a Department of Interventional Oncology ; Renji Hospital; School of Medicine; Shanghai Jiao Tong University ; Shanghai , China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Chen
authors.affiliation: a Department of Interventional Oncology ; Renji Hospital; School of Medicine; Shanghai Jiao Tong University ; Shanghai , China.|b Department of Pathology ; Yueyang Hospital; Shanghai University of Traditional Chinese Medicine ; Shanghai , China.
authors.forename: Shou-Mei
authors.initials: SM
authors.lastname: Wang
authors.affiliation: a Department of Interventional Oncology ; Renji Hospital; School of Medicine; Shanghai Jiao Tong University ; Shanghai , China.
authors.forename: Dong-Juan
authors.initials: DJ
authors.lastname: Xing
authors.affiliation: c Department of Pathology ; Changhai Hospital and Institute of Liver Diseases; Second Military Medical University ; Shanghai , China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhu
authors.affiliation: b Department of Pathology ; Yueyang Hospital; Shanghai University of Traditional Chinese Medicine ; Shanghai , China.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: a Department of Interventional Oncology ; Renji Hospital; School of Medicine; Shanghai Jiao Tong University ; Shanghai , China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; C560103:MIRN622 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C117090:MAP4K4 protein, human; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: MAP4K4; hepatocellular carcinoma; miR-622; microRNA; therapeutic target