期刊
CELL PROLIFERATION
卷 52, 期 3, 页码 -出版社
WILEY
DOI: 10.1111/cpr.12573
关键词
LncRNA Riken; miR-467a-3p; miRNA-96; neural differentiation; Sox6
类别
资金
- National Natural Science Foundation of China [81771132, 81801067, 81870818, 81571028, 16XD1401800]
- Natural Science Foundation of Shanghai [17ZR1416400, 17DZ1205403]
- China Postdoctoral Science Foundation Grant [2018M630472]
- Program of Shanghai Subject Chief Scientist [16XD1401800]
- Shanghai Jiaotong University School of Medicine [TM201715]
Objectives Long non-coding RNAs (LncRNAs) play important roles in epigenetic regulatory function during the development processes. In this study, we found that through alternative splicing, LncRNA C130071C03Riken variants Riken-201 (Riken-201) and Riken-203 (Riken-203) are both expressed highly in brain, and increase gradually during neural differentiation. However, the function of Rik-201 and Rik-203 is unknown. Materials and methods Embryonic stem cells (ESCs); RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over-expression and RNA interference of genes; flow cytometry; real-time quantity PCR; and Western blot were used in the studies. RNA pull-down assay and PCR were employed to detect any miRNA that attached to Rik-201 and Rik-203. The binding of miRNA with mRNA of Sox6 was presented by the luciferase assay. Results Repression of Rik-201 and Rik-203 inhibited neural differentiation from mouse embryonic stem cells. Moreover, Rik-201 and Rik-203 functioned as the competing endogenous RNA (ceRNA) to repress the function of miR-96 and miR-467a-3p, respectively, and modulate the expression of Sox6 to further regulate neural differentiation. Knockout of the Rik-203 and Rik-201 induced high ratio of brain developmental retardation. Further we found that C/EBP beta might potentially activated the transcription of Rik-201 and Rik-203. Conclusions These findings identify the functional role of Rik-201 and Rik-203 in facilitating neural differentiation and further brain development, and elucidate the underlying miRNAs-Sox6-associated molecular mechanisms.
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