Elevated PTPN3 expression in type 2 diabetes mellitus: Insights from genetic and experimental analyses

Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia, leading to severe complications, including increased risk of cancer. Protein tyrosine phosphatase non-receptor type 3 (PTPN3) is implicated in both T2DM and cancer progression. The aim of the present study was to investigate the role of PTPN3 genetic polymorphisms and expression in patients with T2DM, as well as to examine changes in body weight, blood glucose levels, and hepatic PTPN3 expression in <i>db/db</i> obese mice in comparison with control mice at 4, 16 and 32 weeks. A total of 469 patients with T2DM and 1,699 healthy control subjects were analyzed for PTPN3 genetic polymorphisms using blood samples. Additionally, the body weight of genetically diabetic obese <i>db/db</i> mice and genotype control mice, and their fasting blood glucose and PTPN3 mRNA and protein expression levels were assessed in the respective liver tissues at different stages of T2DM progression (4, 16 and 32 weeks) using reverse transcription-quantitative PCR, western blot and immunohistochemistry staining analyses. The allele C frequency of rs75235286 (82.1 vs. 79.1%, P=0.044) and allele G frequency of rs17202063 (82.8% vs. 79.5%, P=0.027) in PTPN3 SNPs differed significantly between T2DM patients and healthy controls. Additionally, the body weight of <i>db/db</i> mice and blood glucose levels were significantly increased from the 4th to 32nd week compared with control mice. Furthermore, <i>db/db</i> mice exhibited significantly elevated hepatic mRNA and protein expression levels of PTPN3 compared with control mice, especially at the 32nd week. Taken together, these findings suggested that an increased level of PTPN3 expression may serve a role in the progression of diabetic complications in patients with T2DM, highlighting the importance of further investigation into PTPN3 as a potential therapeutic target to decrease cancer risk and enhance treatment outcomes in T2DM.