AK048794 maintains the mouse embryonic stem cell pluripotency byfunctioning as miRNA sponges for miR-592.

AK048794 maintains the mouse embryonic stem cell pluripotency byfunctioning as miRNA sponges for miR-592.
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AK048794 通过充当 miR-592 的 miRNA 海绵来维持小鼠胚胎干细胞的多能性。

DOI:
10.1042/bcj20160540
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发表时间:
2016
期刊:
Biochem J.
影响因子:
--
通讯作者:
Jing Zhang
Jing Zhang
中科院分区:
其他
文献类型:
--
作者:
Yang Zhou;Qing-Song Dai;Shi-Chang Zhu;Yue-Hua Han;Hai-Long Han;Bo Zhao;Rong-Rong Gao;Jun Zhang;Jing Zhang

文献摘要

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MiR-592是一种富含神经元的microRNA,在mNPCs的分化过程中起重要作用,在体外可诱导星形胶质细胞分化阻滞或/和促进神经元的发生。以往的研究表明,长链非编码RNA(lncRNA)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,我们采用基因芯片技术检测了miR-592基因敲除小鼠胚胎干细胞(mESCs)和相应正常mESCs中lncRNA的表达谱。通过微阵列分析和荧光素酶报告基因分析,我们证明了受转录因子GATA 1调控的lncRNA-AK 048794作为miR-592的竞争性内源性RNA(ceRNA)发挥作用,并导致其内源性靶点FAM 91 A1的去抑制,FAM 91 A1参与mESC多能性维持。综上所述,这些观察结果表明,AK 048794通过充当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miRNA网络与mESC多能性之间的联系。
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 neurogenesisin 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.