miR-765 targeting PDX1 impairs pancreatic β-cell function to induce type 2 diabetes

Abstract

Type 2 diabetes (T2DM) is a chronic metabolism disorder with a symptom as pancreatic β-cell dysfunction. In this study, the bioinformatics analysis identified the key regulators (PDX1 and miR-765) in T2DM. By qRT-PCR and western blotting, miR-765 with high expression and PDX1 with low expression were observed in blood samples from T2DM patients and the T2DM cell model. Together with GSIS assay, CCK-8, TUNEL assay, glycolysis assay, and mitochondrial respiration assay, miR-765 overexpression impaired insulin secretion cell viability, glycolysis, and mitochondrial respiration, while enhanced cell apoptosis in pancreatic β-cell. The Luciferase reporter, RIP, and RNA pull-down assays showed that PDX1 was the target gene of miR-765 in pancreatic β-cell. Besides, the negative effect of miR-765 on pancreatic β-cell could be overturned by PDX1 overexpression. In conclusion, we confirmed that miR-765 could cause a detrimental effect on pancreatic β-cell survival and function by targeting PDX1, which might provide new insight for T2DM therapy.

Keywords:

• PDX1
• miR-765
• pancreatic β-cell
• type 2 diabetes
• apoptosis

Ethical approval and consent to participate

This study gained approval from the Ethics Committee of Wuhan Wuchang Hospital Affiliated to Wuhan University of Science and Technology and performed in keeping with the Declaration of Helsinki. Written informed consent from all subjects was obtained before sampling.

Author contributions

LZ and YLW conducted the study, collected and analysed the data. YL designed the study and methods and collected the funds. YHL analysed and interpreted the data. LL collected materials and resources, conducted literature analysis, and prepared manuscript. XHW conducted the literature analysis and prepared the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the General Project of Joint Fund of Health and Family Planning Commission of Hubei Province [WJ2018H0122] and by the Project of Natural Science Foundation of Hubei Province.