Mir-153 As a Tumor Suppressor in Glioblastoma Multiforme Is Downregulated by Dna Methylation Publisher Pubmed



Ghasemi A¹ ; Fallah S^{2, 3} ; Ansari M¹
Source: Clinical Laboratory Published:2016

Abstract

Background: Aberrant DNA hypermethylation contributes to many cancers by silencing structurally normal tumor suppressive genes. MicroRNA-153 (miR-153) exerts a tumor suppressive function in glioblastoma multiforme (GBM) by silencing oncogenic targets. However, the mechanism underlying miR-153 regulation in glioma cells has not been studied. Methods: The expression levels of miR-153 were determined by real-time PCR and genomic bisulfite modification technique was used to detect the DNA methylation status in the upstream region of miR-153 in GBM, their matched normal adjacent tissues, and the glioblastoma U87 cell line. Following treatment of cells with 5-aza-2'-deoxy-citidine (5-aza-dC), the DNA methylation, gene expression and target proteins levels of miR-153 were determined. Results: This study confirmed that miR-153 is significantly downregulated and hypermethylated in GBM tissues compared to their matched normal adjacent tissues. Increased methylation level of miR-153 was significantly correlated with reduced miR-153 expression in GBM tissue specimens. Demethylation of cells by 5-aza-dC treatment led to reduction of miR-153 methylation level, re-expression of candidate microRNA, and downregulation of its target proteins levels. Conclusions: Our data indicated that miR-153 acts as a tumor suppressor in GBM and is down-regulated by DNA methylation, suggesting that miR-153 may serve as a potential diagnostic or therapeutic target of GBM.