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学科主题基础医学
MiR-499 Regulates Cell Proliferation and Apoptosis during Late-Stage Cardiac Differentiation via Sox6 and Cyclin D1
Li, Xianhui1; Wang, Jiaji1; Jia, Zhuqing1; Cui, Qinghua2; Zhang, Chenguang1; Wang, Weiping1; Chen, Ping1; Ma, Kangtao1; Zhou, Chunyan1
刊名PLOS ONE
2013-09-11
DOI10.1371/journal.pone.0074504
8期:9
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Natural Science Foundation of Beijing, China ; Leading Academic Discipline Project of Beijing Education Bureau ; 111 Project of China ; National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Natural Science Foundation of Beijing, China ; Leading Academic Discipline Project of Beijing Education Bureau ; 111 Project of China
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]DOWN-REGULATION ; EXPRESSION ; HEART ; GENE ; REGENERATION ; MICRORNA ; DEATH
英文摘要

Background: MiR-499 is a cardiac-abundant miRNA. However, the biological functions of miR-499 in differentiated cardiomyocytes or in the cardiomyocyte differentiation process is not very clear. Sox6 is believed to be one of its targets, and is also believed to play a role in cardiac differentiation. Therefore, our aim was to investigate the association between Sox6 and miR-499 during cardiac differentiation.

Methodology/Principal Findings: Using a well-established in vitro cardiomyocyte differentiation system, mouse P19CL6 cells, we found that miR-499 was highly expressed in the late stage of cardiac differentiation. In cells stably transfected with miR-499 (P-499 cells), it was found that miR-499 could promote the differentiation into cardiomyocytes at the early stage of cardiac differentiation. Notably, cell viability assay, EdU incorporation assay, and cell cycle profile analysis all showed that the P-499 cells displayed the distinctive feature of hyperplastic growth. Further investigation confirmed that miR-499 could promote neonatal rat cardiomyocyte proliferation. MiR-499 knockdown enhanced apoptosis in the late differentiation stage in P19CL6 cells, but overexpression of miR-499 resulted in a decrease in the apoptosis rate. Sox6 was identified as a direct target of miR-499 and its expression was detected from day 8 or day 10 of cardiac differentiation of P19CL6 cells. Sox6 played a role in cell viability, inhibited cell proliferation and promoted cell apoptosis in P19CL6 cells and cardiomyocytes. The overexpression of Sox6 could reverse the proliferation and anti-apoptosis effects of miR-499. It was also found that miR-499 might exert its function by regulating cyclin D1 via its influence on Sox6.

Conclusions/Significance: miR-499 probably regulates the proliferation and apoptosis of P19CL6 cells in the late stage of cardiac differentiation via its effects on Sox6 and cyclin D1.

语种英语
所属项目编号81070112 ; 81071675 ; 81170713 ; 20110001130001 ; 5122021 ; B07001
资助者National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Natural Science Foundation of Beijing, China ; Leading Academic Discipline Project of Beijing Education Bureau ; 111 Project of China ; National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Natural Science Foundation of Beijing, China ; Leading Academic Discipline Project of Beijing Education Bureau ; 111 Project of China
WOS记录号WOS:000326734500098
引用统计
被引频次:26[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/68107
专题北京大学基础医学院
作者单位1.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Key Lab Mol Cardiovasc Sci,Minist Educ China, Beijing 100871, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Biomed Informat, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Li, Xianhui,Wang, Jiaji,Jia, Zhuqing,et al. MiR-499 Regulates Cell Proliferation and Apoptosis during Late-Stage Cardiac Differentiation via Sox6 and Cyclin D1[J]. PLOS ONE,2013,8(9).
APA Li, Xianhui.,Wang, Jiaji.,Jia, Zhuqing.,Cui, Qinghua.,Zhang, Chenguang.,...&Zhou, Chunyan.(2013).MiR-499 Regulates Cell Proliferation and Apoptosis during Late-Stage Cardiac Differentiation via Sox6 and Cyclin D1.PLOS ONE,8(9).
MLA Li, Xianhui,et al."MiR-499 Regulates Cell Proliferation and Apoptosis during Late-Stage Cardiac Differentiation via Sox6 and Cyclin D1".PLOS ONE 8.9(2013).
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