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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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- 학술저널
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- 2015.1
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Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2′-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.
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참고문헌 (25)
참고문헌 신청
Agirre X / 2009 / Epigenetic silencing of the tumor suppressor microRNA HsamiR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia /
Bashtrykov P / 2015 / DNMT1-associated DNA methylation changes in cancer / Cell Cycle 14 : 5 ~
Cacan E / 2014 / Inhibition of HDAC1 and DNMT1 modulate RGS10 expression and decrease ovarian cancer chemoresistance / PLoS One 9 : e87455 ~
Chai H / 2011 / miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines / Acta Biochim Biophys Sin 43 : 217
Codo P / 2014 / MicroRNAmediated down-regulation of NKG2D ligands contributes to glioma immune escape / Oncotarget 5 : 7651 ~ 7662
Bashtrykov P / 2015 / DNMT1-associated DNA methylation changes in cancer / Cell Cycle 14 : 5 ~
Cacan E / 2014 / Inhibition of HDAC1 and DNMT1 modulate RGS10 expression and decrease ovarian cancer chemoresistance / PLoS One 9 : e87455 ~
Chai H / 2011 / miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines / Acta Biochim Biophys Sin 43 : 217
Codo P / 2014 / MicroRNAmediated down-regulation of NKG2D ligands contributes to glioma immune escape / Oncotarget 5 : 7651 ~ 7662
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