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 b-TC-tet (pancreatic b 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 b-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 b-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 b-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. (Endokrynol Pol 2020; 71 (5): 404-410

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

“…Whole milk collected within month 2 of lactation from mothers of preterm infants showed stable expression of miR-16 and miR-21 [ 386 ]. Notably, miR-16-5p inhibits the apoptosis of high glucose-induced pancreatic β cells via targeting of chemokine with CXC motif ligand 10 [ 387 ]. Circulating serum levels of miR-16-5p were upregulated in women with gestational diabetes [ 388 ].…”

Progression of Type 1 Diabetes: Circulating MicroRNA Expression Profiles Changes from Preclinical to Overt Disease

“…It seems to favor Treg induction [ 22 , 25 ], which is highly expressed in beta cells, and negatively regulates the protein Ptch1 (protein patched homolog 1) involved in the inhibition of beta cell proliferation [ 30 ]. miR-16 seems to protect from high glucose-induced pancreatic beta cell apoptosis by targeting CXCL10 [ 31 ] and from immune aggression as it was negatively correlated with ZnT8A levels in our cohort ( r = −0.358; p = 0.044). The most enriched pathways for miR-16 predicted targets were related to cell cycle regulation and division, checkpoint control, and DNA repair ( Figure 7 ).…”

miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus

“…These proteins are crucial factors in a proper insulin signaling pathway, and their downregulation results in insulin resistance and metabolic disorders like diabetes. Additionally, miR-16-5p-targeted genes are involved in pancreatic β-cell proliferation and apoptosis ( 39 ). Target genes for miR-16-5p that are downregulated in type 2 diabetes are located in not only β-cells on pancreatic islets, but also peripheral blood mononuclear cells (PBMCs), the liver, and skeletal muscle ( 40 ).…”