Analysis of Up-Regulation of DNA-PKcs and Its Mechanism in Human Gliomas

Abstract

OBJECTIVE To detect the differences in gene expression of nonhomologous end-joining pathway including Ku70, Ku80, ERCC4, lig4 and DNA-PKcs between human primary gliomas and normal brain tissues, and furthermore, to explore the underlying mechanism for the expression alteration. METHODS The expression levels of Ku70, Ku80, ERCC4, lig4 and DNA-PKcs in 36 specimens of glioma and 12 specimens of normal brain tissue were measured using SYBR green-based real-time quantitative PCR. Methylation of DNA-PKcs was detected through methylation-specifi c PCR (MSP). RESULTS There was no significant difference in expression of Ku70, Ku80, ERCC4 and lig4 between human primary gliomas and normal brain tissues (P < 0.05), while DNA-PKcs were significantly up-regulated (P = 0.002). The expression of DNA-PKcs was significantly higher in patients with grade III and IV diseases compared to patients with grade II disease or in normal brain tissues (P < 0.05). Moreover, glioma tissue showed weaker methylation than normal brain tissue. CONCLUSION The up-regulation of the DNA-PKcs may be associated with pathogenesis of glioma. Demethylation of DNA-PKcs promoter is an important reason for its up-regulation.

Keywords

• glioma
• non-homologous end joining
• NHEJ
• DNA-PKcs
• methylation
• real-time PCR.