Key Laboratory of Oral Diseases of Jiangsu Province and Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China; Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Key Laboratory of Oral Diseases of Jiangsu Province and Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China; Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Exp Cell Res. 2019 Oct 15;383(2):111562. doi: 10.1016/j.yexcr.2019.111562. Epub 2019 Aug 19.
Biological phenotypes of mesenchymal stem cells (MSCs) are regulated by a series of biochemical elements, including microRNAs, hormones and growth factors. Our previous study illustrated a significant role of miR-141-3p during the osteogenic differentiation of stem cells from apical papilla (SCAPs). Nevertheless, the functions of miR-141-3p in regulating the proliferative ability and senescence of SCAPs have not been determined. This study identified that overexpression of miR-141-3p inhibited the proliferative ability of SCAPs. Meanwhile, the senescence of SCAPs was ahead of time. Conversely, transfection of miR-141-3p inhibitor promoted the proliferative ability of SCAPs and delayed their senescence. Yes-associated protein (YAP) was predicted as the downstream target gene of miR-141-3p by online softwares (miRDB, miRTarBase, miRWalk, and TargetScan), and was further verified by dual-luciferase reporter gene assay. Additionally, knockdown of YAP inhibited the proliferation and accelerated the senescence of SCAPs. Collectively, these findings proposed a novel direction that miR-141-3p impeded proliferative ability and promoted senescence of SCAPs through post-transcriptionally downregulating YAP.
间充质干细胞 (MSCs) 的生物学表型受一系列生化因素的调节,包括 microRNAs、激素和生长因子。我们之前的研究表明,miR-141-3p 在根尖乳头干细胞 (SCAPs) 的成骨分化过程中发挥重要作用。然而,miR-141-3p 在调节 SCAPs 的增殖能力和衰老方面的功能尚未确定。本研究发现,过表达 miR-141-3p 抑制了 SCAPs 的增殖能力。同时,SCAPs 的衰老提前了。相反,转染 miR-141-3p 抑制剂促进了 SCAPs 的增殖能力并延缓了其衰老。在线软件(miRDB、miRTarBase、miRWalk 和 TargetScan)预测 Yes 相关蛋白 (YAP) 是 miR-141-3p 的下游靶基因,并通过双荧光素酶报告基因检测进一步验证。此外,敲低 YAP 抑制了 SCAPs 的增殖并加速了其衰老。总之,这些发现提出了一个新的方向,即 miR-141-3p 通过转录后下调 YAP 来阻碍 SCAPs 的增殖能力并促进其衰老。