title: MicroRNA-362-5p promotes tumor growth and metastasis by targeting CYLD in hepatocellular carcinoma.
abstract: MicroRNAs are increasingly recognized as playing important roles in hepatocellular carcinoma (HCC) tumorigenesis. Here we identified an essential role for miR-362-5p in the regulation of HCC development. We found that miR-362-5p was significantly up-regulated in HCCs and associated with HCC progression. Inhibition of miR-362-5p in HCC cells dramatically decreased cell proliferation, clonogenicity, migration and invasion in vitro as well as tumor growth and metastasis in vivo. We subsequently identified that CYLD was a target gene of miR-362-5p. Furthermore, knockdown of CYLD expression partially counteracted the tumor suppressive effects of miR-362-5p inhibitors. Finally, we have shown that miR-362-5p acts through CYLD to activate the NF-κB signaling pathway, which contributes to HCC progression. Taken together, our findings indicate that miR-362-5p belongs to a new class of oncomiR that regulates HCC cell aggressiveness, thus providing new insight into the molecular mechanisms underlying HCC development. This study also suggests that miR-362-5p may serve as a novel therapeutic target for miRNA based HCC therapy.
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China; Institute of Immunology, School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei 230027, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ni
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Huaqin
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Pathology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Experimental Animal Center, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Zhongqian
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei 230027, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China.
authors.forename: Danlei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei 230027, China. Electronic address: ustcwhm@ustc.edu.cn.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology, Anhui Medical University, 81 Mei-Shan Road, Hefei 230032, China. Electronic address: sywang@ahmu.edu.cn.
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D000074749:Deubiquitinating Enzyme CYLD; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C581582:MIRN362 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: CYLD; Hepatocellular carcinoma; Metastasis; miR-362-5p