miRNA-16-5p inhibits the apoptosis of high glucose-induced pancreatic β cells via targeting of CXCL10: Potential biomarkers in type 1 diabetes mellitus

Abstract

Introduction: We aimed to elucidate the relationship between CXC chemokine ligand 10 (CXCL10) and miR-16-5p, and their functions on the biological behaviour of type 1 diabetes mellitus (T1DM). Material and methods: The GSE72492 dataset from the GEO database was used to analyse gene expression. We discovered that CXCL10 was highly expressed in T1DM patients. The up-stream miRNA was predicted by Targetscan website. Low glucose (2.8 mmol/L) and high glucose (HG, 16.7 mmol/L) were utilised to treat β-TC-tet (pancreatic β cell) cells to form the model. The direct interaction between miR-16-5p and CXCL10 was verified by a dual-luciferase reporter assay. Real-time quantitative PCR (qRT-PCR) and western blotting analyses were used to detect RNA and protein expression. CCK8 and flow cytometry were used to detect cell proliferation and apoptosis. Results: We discovered that CXCL10 was highly expressed in T1DM patients. MiR-16-5p, which was lowly expressed in T1DM patients, was verified the upstream regulatory miRNA of CXCL10. The facilitating influence of miR-16-5p up-regulation on the proliferation of HG-induced β-TC-tet cells was reversed by CXCL10 over-expression, while the knockdown results were opposite. More importantly, the restraining impact of miR-16-5p high expression on the apoptosis of HG-induced β-TC-tet cells was accelerated by CXCL10 over-expression. Correspondingly, the level of Bcl-2 was enhanced while the levels of Bax and Cleaved Caspase-3 were lowered by miR-16-5p mimic, which were reversed by CXCL10 over-expression in HG-treated β-TC-tet cells. Conclusions: Our data offered evidence that miR-16-5p implicated in T1DM cell proliferation and apoptosis through targeting CXCL10, which might provide novel therapeutic information for T1DM.