miR-4651 inhibits cell proliferation of gingival mesenchymal stem cells by inhibiting HMGA2 under nifedipine treatment  

作　　者：Xiao Han Ruzhuang Yang Haoqing Yang Yangyang Cao Nannan Han Chen Zhang Ruitang Shi Zhengting Zhang Zhipeng Fan 

机构地区：[1]Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction,Beijing Stomatological Hospital,School of Stomatology,Capital Medical University,Beijing,China [2]Department of Prosthodontics,Beijing Stomatological Hospital,School of Stomatology,Capital Medical University,Beijing,China [3]Department of Stomatology,First Hospital of Qinhuangdao,Qinhuangdao,China [4]Department of Periodontology,Beijing Stomatological Hospital,School of Stomatology,Capital Medical University,Beijing,China [5]Department of Endodontics,Beijing Stomatological Hospital,School of Stomatology,Capital Medical University,Beijing,China

出　　处：《International Journal of Oral Science》2020年第2期132-141,共10页国际口腔科学杂志（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(81625005 to Z.P.F.);the Program for“Hundred-Thousand-Ten thousand”Talents in Beijing(2018A16 to Z.P.F.)。

摘　　要：Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells(GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra(SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2(HMGA2) is the downstream target gene of mi R-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that mi R-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of mi R-4651 and HMGA2 as therapeutic targets.

关 键 词：HMGA2 GINGIVAL INHIBITING 

分 类 号：R96[医药卫生—药理学]