title: VCP/p97, down-regulated by microRNA-129-5p, could regulate the progression of hepatocellular carcinoma.
abstract: Valosin containing protein (VCP)/p97 plays various important roles in cells. Moreover, elevated expression of VCP in hepatocellular carcinoma (HCC) is correlated with increased incidence of recurrence. But the role of VCP in HCC progression in vitro and in vivo is unclear. And there are few reports about the regulation mechanism on the expression of VCP in HCC. In this study, it was identified that the level of VCP was frequently increased in human HCC tissues. In addition, down-regulation of VCP with siRNAs could dramatically suppress the genesis and progression of tumor in vivo. It was found that miR-129-5p directly inhibited the expression of VCP in several HCC cell lines. Meanwhile, the level of VCP in HCC tissues was negatively associated with the level of miR-129-5p. Our further investigation showed that the enhanced expression of miR-129-5p also suppressed tumor growth in vivo. Moreover, it was revealed that miR-129-5p could inhibit the degradation of IκBα and increase the apoptosis and reduce the migration of HCC cells by suppressing the expression of VCP. Our results revealed that the expression of VCP was directly regulated by miR-129-5p and this regulation played an important role in the progression of HCC.
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Hei
authors.forename: Qingming
authors.initials: Q
authors.lastname: Shu
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Yaping
authors.initials: Y
authors.lastname: Gao
authors.forename: Hanjiang
authors.initials: H
authors.lastname: Fu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zheng
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D015398:Signal Transduction; D047368:Tumor Burden; D057149:Ubiquitinated Proteins / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D016328:NF-kappa B; D057149:Ubiquitinated Proteins; D051550:I-kappa B Kinase; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse