title: MiR-223 regulates human embryonic stem cell differentiation by targeting the IGF-1R/Akt signaling pathway.
abstract: 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.
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Deng-Shu
authors.initials: DS
authors.lastname: Wu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Liang
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.forename: Fang-Ping
authors.initials: FP
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D053595:Embryonic Stem Cells; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D005346:Fibroblast Growth Factors; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; C525067:MIR223, human