miR-708-5 p 通过抑制 TMEM88表达促进人骨髓间充质干细胞迁移

摘要

AIM: To investigate the effect of microRNA-708-5p (miR-708-5p) on the migration of human mesenchymal stem cells (hMSCs).METHODS:The expression of miR-708-5p was determined by miRNA arrays and re-al-time PCR.By transfection of miR-708-5p mimic or inhibitor, the up-regulation or down-regulation of miR-708-5p ex-pression in hMSCs was evaluated .The cell scratch and Transwell tests were used to detect the migration capability of hM-SCs.The effects of transmembrane protein 88 (TMEM88), a miR-708-5p target gene, onβ-catenin expression and migra-tion of hMSCs were detected .RESULTS:The expression of miR-708-5p was down-regulated in the old hMSCs compared with the young hMSCs.Up-regulation of miR-708-5p resulted in increasing migration of hMSCs.Conversely, down-regula-tion of miR-708-5p resulted in decreasing cell migration .The expression of TMEM88 was up-regulated in the old hMSCs compared with the young hMSCs , while the expression of β-catenin was down-regulated.Directly repression of TMEM88 expression increased the β-catenin expression and migration of hMSCs .The regulation of miR-708-5p on hMSCs was atten-uated by inhibiting the expression of miR-708-5p and TMEM88 together.CONCLUSION:miR-708-5p increases β-cate-nin expression and Wnt/β-catenin activity by repressing TMEM 88, thus enhancing the migration of hMSCs .%目的：研究年龄相关microRNA－708－5p（miR－708－5p）对人骨髓间充质干细胞（hMSCs）迁移能力的调控作用。方法：通过microRNA芯片和real－time PCR检测供体年龄对hMSCs 中miR－708－5p表达的影响；通过转染miR－708－5p模拟物或抑制物，过表达或抑制miR－708－5p表达；通过细胞划痕及Transwell实验检测hMSCs迁移能力。通过siRNA研究miR－708－5p靶基因跨膜蛋白88（TMEM88）对hMSCs 中β链球蛋白（β－catenin）及hMSCs迁移功能的影响。结果：随供体年龄增加，hMSCs 中miR－708－5p的表达下降。过表达miR－708－5p可促进hMSCs迁移。相反，抑制miR－708－5p的表达可减少hMSCs迁移。随供体年龄增加，TMEM88表达增加，而β－catenin表达下降，直接抑制TMEM88的表达可促进β－catenin表达，促进hMSCs迁移。同时抑制miR－708－5p和TMEM88，使miR－708－5p失去对hMSCs的调控作用。结论：miR－708－5p可通过抑制TMEM88表达，上调β－catenin，从而活化Wnt／β－catenin信号通路，促进hMSCs迁移。