南方医科大学学报2021，Vol.41Issue(8)：1125-1130,6.DOI:10.12122/j.issn.1673-4254.2021.08.01
小核非编码RNA 7SK 128-179截短体通过下调CDC6抑制胚胎干细胞的体外增殖
7SK truncation at 128-179 nt suppresses embryonic stem cell proliferation in vitro by downregulating CDC6
摘要
Abstract
Objective To explore the role of small nuclear noncoding RNA 7SK in embryonic stem cell (ESCs) proliferation and the value of 7SK as a target for early diagnosis and treatment for primordial dwarfism (PD). Methods ESC line R1 was transfected with the CRISPR/Cas9 system, and sequencing of the PCR product and glycerol gradient analysis were performed to identify novel 7SK deletion mutations. A lentivirus system was used to knock down cyclin-dependent kinase 9 (CDK9) in clones with 7SK deletion mutations, and the effect of CDK9 knockdown on the protein level of cell division cycle 6 (CDC6) was analyzed with Western blotting. Results We identified a novel deletion mutation of 7SK at 128-179 nt in the ESCs, which resulted in deficiency of cell proliferation. 7SK truncation at 128-179 nt significantly reduced the protein expressions of La-related protein 7 (LARP7) and CDC6. Conclusions 7SK truncation at 128-179 nt can significantly impair proliferation of ESCs by downregulating CDC6. 7SK is a key regulator of proliferation and mediates the growth of ESCs through a mechanism dependent on CDK9 activity, suggesting the value of 7SK truncation at 128-179 nt as a potential target for early diagnosis and treatment of PD.关键词
7SK截短体/胚胎干细胞/增殖/周期蛋白依赖激酶9/细胞分裂周期蛋白6Key words
7SK truncation/embryonic stem cell/proliferation/cyclin-dependent kinase 9/cell division cycle 6引用本文复制引用
陈蕊,张玉荣,陈鹏,庞依心,李宏宝,陈子溦,张小用,张鸿毅,李武军..小核非编码RNA 7SK 128-179截短体通过下调CDC6抑制胚胎干细胞的体外增殖[J].南方医科大学学报,2021,41(8):1125-1130,6.基金项目
陕西省西安市科技计划项目(2019115213YX007SF040[7]) （2019115213YX007SF040[7]）
陕西省卫生健康科研项目基金(2018D075)Supported by Xi'an Science and Technology Project of ShaanxiProvincial(No.2019115213YX007SF040[7])and HealthResearch Fund Project of Shaanxi Provincial HealthDepartment(No.2018D075). （2018D075）
