Zhou Yang, Dai Qing-Song, Zhu Shi-Chang, Han Yue-Hua, Han Hai-Long, Zhao Bo, Gao Rong-Rong, Zhang Jun, Zhang Jing
Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai 200065, PR China Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200092, PR China.
Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200092, PR China.
Biochem J. 2016 Oct 15;473(20):3639-3654. doi: 10.1042/BCJ20160540. Epub 2016 Aug 12.
MiR-592 has been identified as a neural-enriched microRNA, plays an important role in mNPCs differentiation, could induce astrogliogenesis differentiation arrest or/and enhance neurogenesis in vitro Previous studies showed that long noncoding RNAs (lncRNAs) were involved in the neuronal development and activity. To investigate the role of miR-592 in neurogenesis, we described the expression profile of lncRNAs in miR-592 knockout mouse embryonic stem cells (mESCs) and the corresponding normal mESCs by microarray. By the microarray analysis and luciferase reporter assays, we demonstrated that lncRNA - AK048794, regulated by transcription factor GATA1, functioned as a competing endogenous RNA (ceRNA) for miR-592 and led to the de-repression of its endogenous target FAM91A1, which is involved in mESC pluripotency maintenance. Taken together, these observations imply that AK048794 modulated the expression of multiple genes involved in mESC pluripotency maintenance by acting as a ceRNA for miR-592, which may build up the link between the regulatory miRNA network and mESC pluripotency.
MiR-592已被鉴定为一种在神经细胞中高度富集的微小RNA，在小鼠神经前体细胞（mNPCs）分化中起重要作用，能够在体外诱导星形胶质细胞生成分化停滞或/和增强神经发生。先前的研究表明，长链非编码RNA（lncRNAs）参与神经元的发育和活动。为了研究miR-592在神经发生中的作用，我们通过微阵列描述了miR-592基因敲除小鼠胚胎干细胞（mESCs）和相应正常mESCs中lncRNAs的表达谱。通过微阵列分析和荧光素酶报告基因检测，我们证明了受转录因子GATA1调控的lncRNA - AK048794作为miR-592的竞争性内源RNA（ceRNA）发挥作用，并导致其内源靶标FAM91A1的去抑制，FAM91A1参与mESC多能性的维持。综上所述，这些观察结果表明，AK048794通过作为miR-592的ceRNA来调节参与mESC多能性维持的多个基因的表达，这可能建立了调控性miRNA网络与mESC多能性之间的联系。
