title: Demethylation-mediated miR-129-5p up-regulation inhibits malignant phenotype of osteogenic osteosarcoma by targeting Homo sapiens valosin-containing protein (VCP).
abstract: Previous studies demonstrated that increased Homo sapiens valosin-containing protein (VCP) may be involved in osteosarcoma (OS) metastasis. However, the underlying mechanism of VCP over-expression in OS remains unknown. In the present study, we found a significantly negative correlation between miR-129-5p and VCP protein expression in OS tissues with pulmonary metastasis (Spearman's rho, rs = -0.948). Bioinformatical prediction, Luciferase reporter assay, Western blot, and RT-PCR assays performed on OS cells indicated that VCP is a target of miR-129-5p. In addition, three CPG islands in the region of miR-129-5p promoter were detected by bioinformatical prediction, and significantly higher expression of miR-129-5p and lower methylation level of miR-129-2 gene in OS cells treated with 5-Aza-2'-deoxycytidine (a potent DNA demethylating agent) than in those untreated cells were observed. Furthermore, lower migratory and invasive ability was found in cells with elevated miR-129-5p than in those with decreased miR-129-5p. These findings indicated that increased miR-129-5p may be mediated by demethylation and inhibit OS cell migration and invasion by targeting VCP in OS, and targeting miR-129-5p/VCP signaling pathway may serve as a therapeutic strategy for OS management, although further studies will be necessary.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Yong Wai Zheng Street 17, Nanchang, Jiangxi, 330006, People's Republic of China.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Long
authors.forename: Yun Fei
authors.initials: YF
authors.lastname: Zhou
authors.forename: Ai Fen
authors.initials: AF
authors.lastname: Peng
authors.forename: Zhi Hong
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Xuan Yin
authors.initials: XY
authors.lastname: Chen
authors.forename: Wen Zhao
authors.initials: WZ
authors.lastname: Chen
authors.forename: Jia Ming
authors.initials: JM
authors.lastname: Liu
authors.forename: Shan Hu
authors.initials: SH
authors.lastname: Huang
authors.forename: Zhi Li
authors.initials: ZL
authors.lastname: Liu
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D063646:Carcinogenesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D000077209:Decitabine; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; D001374:Azacitidine