Association Between Proteasome 26S Subunit, Non-ATPase 3 Methylation and Insulin β Cell Apoptosis in Type 2 Diabetic Mellitus

Guiping Huang,1,2,* Guodong He,1,2,* Shaoxian Chen,1 Liping Mai1,2 1Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2Phase I Clinical Trial Research Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liping Mai, Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Email [email protected]: The methylation of PSMD3 and its influence on protein stability and degradation could play a crucial role in the pathogenesis of type 2 diabetes mellitus (T2DM), although the underlying molecular mechanisms are not yet fully understood. This study investigates the molecular and bioinformatic features of PSMD3 methylation in T2DM.Methods: Bioinformatics analyses were conducted on the T2DM database chip. A model of T2DM was established in rat RIN-m5F cells induced by high glucose (HG) concentration. The function of the PSMD3 gene in T2DM was examined through its overexpression. Western blotting was used to detect the expression of PSMD3 and USP14 proteins. Flow cytometry was used to detect cell apoptosis and proliferation.Results: Methylation of PSMD3 was upregulated in the T2DM tissue microarray data and associated with USP14. PSMD3 overexpression reduced apoptosis and enhanced proliferation in HG-treated RIN-m5F cells. In HG-treated RIN-m5F cells, PSMD3 was linked to USP14 inactivation.Conclusion: PSMD3 methylation might potentially influences cell apoptosis and proliferation in T2DM development which might be associated with activating USP14. This study offers an in-depth examination of PSMD3 methylation’s molecular and bioinformatic traits in T2DM, advancing our comprehension of the molecular mechanisms leading to T2DM.Keywords: proteasome 26S subunit, non-ATPase 3, methylation, insulin β cell, apoptosis, type 2 diabetic mellitus