title: MiR-129-2 functions as a tumor suppressor in glioma cells by targeting HMGB1 and is down-regulated by DNA methylation.
abstract: MicroRNA (miRNA) dysregulation is causally related to cancer development and progression, and recent reports have revealed that DNA methylation constitutes an important mechanism for miRNA deregulation in cancer. MiR-129-2 has been reported to be down-regulated and functions as a tumor suppressor in a few human cancers. However, the involvement of miR-129-2 in the pathology of glioma and the mechanism underlying miR-129-2 regulation in glioma cells remain unclear. In this study, we performed quantitative PCR to investigate the level of miR-129-2 in 21 pairs of glioma tumors and matched adjacent tissues and found that miR-129-2 is down-regulated in glioma tumors. In vitro cell growth, apoptosis, cell migration, and invasion assays revealed that miR-129-2 functions as a tumor suppressor in glioma cells. Luciferase reporter assay found that miR-129-2 could directly target high-mobility group box 1 (HMGB1) and inhibit its expression in glioma cells. Methylation-specific PCR found that DNA methylation in upstream regions of miR-129-2 occured more frequently in cancer tissues than in adjacent tissues. Demethylation of miR-129-2 by 5-aza-2'-deoxycytidine treatment and quantitative PCR analysis revealed that miR-129-2 expression is epigenetically regulated in glioma cells. Taken together, our data suggested that miR-129-2 functions as a tumor suppressor in glioma cells by directly targeting HMGB1 and is down-regulated by DNA methylation, which may provide a novel therapeutic strategy for treatment of glioma.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Jun-Qiang
authors.initials: JQ
authors.lastname: Huang
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Liang-Fang
authors.initials: LF
authors.lastname: Shen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human