A 3′UTR-Associated RNA, FLJ11812 Maintains Stemness of Human Embryonic Stem Cells by Targeting miR-4459
A 3′UTR-Associated RNA, FLJ11812 Maintains Stemness of Human Embryonic Stem Cells by Targeting miR-4459
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DOI：
10.1089/scd.2014.0353
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发表时间：
2015-05-01
影响因子：
4
通讯作者：
Miao, JunYing
中科院分区：
文献类型：
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作者：
Lu, Wei;Han, Lei;Miao, JunYing
3 '非翻译区（UTR）相关RNA（uaRNA）在多种生物学过程中发挥重要作用，尤其是在发育过程中。然而，由于它们与编码蛋白质的mRNA重叠，uaRNA很难通过RNA干扰技术进行研究。我们最近发现了一种化学分子，3-苄基-5-（（2-硝基苯氧基）甲基）-二氢呋喃-2（3 H）-酮（3BDO），它可以有效地诱导人胚胎干细胞（hESC）分化，同时选择性地和有效地下调uaRNA FLJ 11812。通过充当竞争性内源RNA，通过3BDO下调FLJ 11812进一步增加hESC中的miR-4459水平。miR-4459可以降低其靶点CDC 20 B和ATG 13的表达，从而通过细胞周期和自噬改变干细胞性。我们的研究结果首次揭示了FLJ 11812在维持hESCs的干细胞性方面发挥了关键作用。这一发现为研究FLJ 11812在早期发育中的作用机制提供了新的线索和有力的工具。
The 3 ' untranslated region (UTR)-associated RNAs (uaRNAs) have important roles in various biological processes, especially in development. However, since they overlap with protein-coding mRNAs, uaRNAs are difficult to study by RNA interference techniques. We recently identified a chemical molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO), that could efficiently induce human embryonic stem cells (hESCs) differentiation, and meanwhile selectively and efficiently downregulate the uaRNA FLJ11812. By acting as a competing endogenous RNA, downregulated FLJ11812 by 3BDO further increased miR-4459 level in hESCs. miR-4459 could decrease the expression of its targets, CDC20B and ATG13, and thus altered stemness via cell cycle and autophagy. Our results revealed that FLJ11812 played a key role in maintenance of stemness of hESCs for the first time. The findings provide new clues and a powerful tool for investigating the action mechanism of FLJ11812 in early development.