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/G1phase 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.

miR‐196b‐5p inhibits proliferation of Wharton's jelly umbilical cord stem cells

“…Many studies show that miRNAs act directly or indirectly on transcripts encoding proteins related to cell proliferation and cell cycle [18]. To find the target of miR‐196b‐5p and further explain its molecular mechanism on WJCMSC proliferation, we conducted SWATH‐MS analysis in miR‐196‐5p inhibitors and the control groups.…”

“…miRNAs are kinds of noncoding single-stranded RNA molecules, which play a significant role in cell proliferation, cell apoptosis, cell cycle and differentiation by inducing target mRNA cleavage or translational inhibition [17][18][19][20]. Previously, our miRNA array data showed that some miRNAs, including miR-196b-5p, were differentially expressed in WJCMSCs, adipose-derived stem cells (ADSCs), BMMSCs, stem cells from apical papilla (SCAPs), dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs), which was confirmed by real-time quantitative RT-PCR (qRT-PCR) ( Fig.…”

miR-140-3p enhanced the osteo/odontogenic differentiation of DPSCs via inhibiting KMT5B under hypoxia condition

“…The levels of miR-140-3p were observed as previously stated. 56 Besides, following the manufacturer’s protocol (Invitrogen), 2 μg RNA sample was reverse transcribed into cDNA. The KMT5B primers are as follows: forward, 5′-GAGAAATGGAGGCAAGTTGTCT-3′; and reverse, 5′-ACATAGCGACTCTGTCCTTCA-3′.…”

“…MiR-140-3p mimic or mimic control along with the wild-type (wt) or mutant (mut) KMT5B 3′UTR-Luc reporter construct was then cotransfected into 293 T cells, as previously stated. 56 48 h later, luciferase enzymatic activities were then detected using the Dual-Luciferase Reporter Assay Kit (Vazyme).…”

“…In short, DPSCs were labelled as previously depicted. 56 A flow cytometry was then used to detect the labeling cells 3 days later. The data was analyzed using MODFIT LT.…”