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Archive > Volume 28 Issue 5 > 2021,28(5):435-442. DOI:10.3872/j.issn.1007-385X.2021.05.003 Prev Next
Basic Research
Role of G protein-coupled receptor kinase 3 in the proliferation, migration and invasion of oral squamous carcinoma cells and its possible mechanism
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Abstract:
[Abstract] Objective: To investigate the effects of silencing G protein-coupled receptor kinase 3 (GRK3) on the proliferation, migration and invasion of oral squamous cell carcinoma (OSCC) cells and the possible underlying mechanisms. Methods: GRK3 expression levels in normal oral tissues and OSCC tissues were analyzed using Oncomine database. RNA interference technology was used to down-regulate GRK3 expression in OSCC cell lines WSU-HN6 and CAL27. The interference efficiency was verified by qPCR. The effects of knockdown of GRK3 on proliferation and apoptosis of OSCC cells were detected by CCK-8 assay and Flow cytometry, respectively; the effects on migration and invasion abilities of OSCC cells were determined by Transwell assay; and the effects on mRNA expression levels of molecules associated with cell cycle, epithelial-mesenchymal transition (EMT), and matrix metallopeptidase (MMP) were determined by qPCR. The changes in protein levels of molecules associated with EMT and MMP were detected using WB assay. Results: GRK3 expression level in OSCC tissues was significantly higher than that in normal oral tissues ( P<0.01). After being transfected with si-GRK3, the mRNA expression of GRK3 in OSCC cells was down-regulated by more than 70%. Silencing GRK3 significantly inhibited the proliferation, migration and invasion of OSCC cells (all P<0.01), but had no significant effect on apoptosis (P>0.05). After down-regulation of GRK3, the percentage of OSCC cells in G0/G1 phase was significantly increased (P<0.01); the mRNA expression levels of Cyclin D1, Cyclin D3, CDK2 and CDK4 were decreased (all P<0.05); expression levels of EMT-related proteins (Vimentin, Zeb1 and Slug) were decreased, while E-cadherin was increased (all P<0.05); MMP3 and MMP9 were decreased (all P<0.05), while MMP2 and MMP7 showed no significant changes (all P>0.05). Conclusion: GRK3 promotes the proliferation of OSCC cells by regulating cell cycle-related molecules and enhances the migration and invasion through regulating EMT and MMPs.
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Project Supported:
Project supported by the Young Medical Talents-Clinical Laboratory Projects of Shanghai “Rising Stars of Medical Talent” Youth Development Program (No. Shanghai Municipal Health Personnel [2020] 087), and the Basic Research Boost Program of the Fundamental Research Program Funding of Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (No. JYZZ040)
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