MiR-223 regulates human embryonic stem cell differentiation by targeting the IGF-1R/Akt signaling pathway.
MiR-223 regulates human embryonic stem cell differentiation by targeting the IGF-1R/Akt signaling pathway.
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MiR-223 通过靶向 IGF-1R/Akt 信号通路调节人胚胎干细胞分化
DOI：
10.1371/journal.pone.0078769
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen FP
中科院分区：
文献类型：
--
作者：
Yu YH;Zhang L;Wu DS;Zhang Z;Huang FF;Zhang J;Chen XP;Liang DS;Zeng H;Chen FP
目前，存在与培养多能人类胚胎干细胞（hESC）相关的困难，并且关于其调节机制的知识有限。microRNAs（miRNAs）调控基因表达，在干细胞自我更新和分化中发挥重要作用。此外，成纤维细胞生长因子（FGF）和胰岛素样生长因子受体（IGF-1 R）是hESC中信号传导的关键激活剂。基于miR-223和IGF-1 R mRNA互补结合位点的鉴定，提出miR-223作为IGF-1 R的局部调节剂。因此，在分化的hESC与未分化的hESC中检测到miR-223的水平。此外，在这两个hESC群体中测定增殖、凋亡和分化，并在存在外源性miR-223和miR-223抑制剂的情况下进行比较。发现抑制miR-223可维持hESC的未分化状态，而添加miR-223可诱导分化。此外，发现这些作用可能依赖于IGF-1 R/Akt信号传导。
Currently, there are difficulties associated with the culturing of pluripotent human embryonic stem cells (hESCs), and knowledge regarding their regulatory mechanisms is limited. MicroRNAs (miRNAs) regulate gene expression and have critical functions in stem cell self-renewal and differentiation. Moreover, fibroblast growth factor (FGF) and the insulin-like growth factor receptor (IGF-1R) are key activators of signaling in hESCs. Based on the identification of complementary binding sites in miR-223 and IGF-1R mRNA, it is proposed that miR-223 acts as a local regulator of IGF-1R. Therefore, levels of miR-223 were detected in differentiated versus undifferentiated hESCs. In addition, proliferation, apoptosis, and differentiation were assayed in these two hESC populations and were compared in the presence of exogenous miR-223 and miR-223 inhibitor. Inhibition of miR-223 was found to maintain the undifferentiated state of hESCs, while addition of miR-223 induced differentiation. Furthermore, these effects were found to be likely dependent on IGF-1R/Akt signaling.
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