Exosomal miR-19a decreases insulin production by targeting Neurod1 in pancreatic cancer associated diabetes

• Published in: Molecular biology reports Vol. 49; no. 3; pp. 1711 - 1720
• Main Authors: Su, Jiaojiao, Pang, Wenjing, Zhang, Aisen, Li, Lei, Yao, Weiyan, Dai, Xin
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-03-2022; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Beta cells; Beta2 protein; Biomedical and Life Sciences; Diabetes; Diabetes mellitus; Diabetes Mellitus - metabolism; Exosomes; Exosomes - genetics; Exosomes - metabolism; Histology; Humans; Insulin; Insulin - metabolism; Insulin secretion; Insulin-Secreting Cells - metabolism; Life Sciences; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Morphology; Original Article; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pathogenesis; Secretions; Pancreatic neoplasm; Exosome; miR-19a; β cell dysfunction
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06980-z

Background
New onset diabetes mellitus demonstrates a roughly correlation with pancreatic cancer (PaC), which is unique in PaC and was named as PaC-induced DM, but the inner mechanism remains unclear. Exosomes mediate intercellular communication and bearing microRNAs might be direct constituent of effect in target cells.
Methods and results
The isolated exosomes from PaC cells were used to treat pancreatic β cells or the primary mice islets, and the glucose stimulated insulin secretions were measured. We validated the exosomal miR-19a from PaC cells to be an important mediator in the down regulation of insulin secretion by targeting
Neurod1
, the validated gene involved in insulin secretion, by using the quantitative real-time PCR, western blot, and promoter luciferase activity. The relative insulin, cAMP and Ca
2+
expressions were also assayed to verify the inverse correlation between cancerous miR-19a and pancreatic islets Neurod1.
Conclusions
Our study indicated that signal changes between cancer cells and β cells via exosomes might be important in the pathogenesis of PaC-induced DM and supplemented the pathogenesis of PaC-induced DM and provide a possible access of PaC screening strategy.