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DNMT1 mediates chemosensitivity by reducing methylation of miRNA-20a promoter in glioma cells
Daoyang Zhou,Yingfeng Wan,Dajiang Xie,Yirong Wang,Junhua Wei,Qingfeng Yan,Peng Lu,Lianjie Mo,Jixi Xie,Shuxu Yang,Xuchen Qi 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-
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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Yao Benxian,Rui Xue,Wang Daoyang,이상엽 한국비교정부학회 2010 한국비교정부학보 Vol.14 No.2
College students’ mental health research in China has entered a phase of rapid development. In the past 20 years, it has reached an unprecedented development, and a lot of relevant studies and reports have emerged. The article has been made in approach of accounting method of documents for the contents of 536 theses collected in “Acta Psychologica Sinica”, “Psychological Science”, and “Psychological Development and Education”, “Applied Psychology”, “Chinese Mental Health Journal”. It took frequency and percentage statistics as main method. It analyzed the research fields, the usage of scales and questionnaires, and the distribution power of research institutions and regions. It found that researches of college students’ mental health mainly focused on the four general fields such as self‐concept and self‐awareness, the external environment and recreational activities, mental illness and physical problems. The fields of research were widely very much, involving all kinds of aspects in psychology, physiology, and society. Mental health professionals should pay more attention to choosing job, interpersonal relationship, psychological guidance and treatment about college students. More and more researchers also start to use the scales and questionnaires which they design of their own. And they should choose samples not only in the cities where they live but also in other places.
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