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

Abstract

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 miR-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 miR-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that miR-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 miR-4651 and HMGA2 as therapeutic targets.

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Funding

National Natural Science Foundation of China (National Science Foundation of China)(81625005 to Z.P.F., 81625005 to Z.P.F., 81625005 to Z.P.F., 81625005 to Z.P.F., 81625005 to Z.P.F., 81625005 to Z.P.F., 81625005 to Z.P.F.)

the Program for “Hundred-Thousand-Ten thousand” Talents in Beijing (2018A16 to Z.P.F.)

École Nationale d'Ingénieurs de Saint-Etienne (National Engineering School of Saint-Étienne)(81625005 to Z.P.F.)