Int J Biol Sci 2021; 17(13):3622-3633. doi:10.7150/ijbs.56271 This issue

Research Paper

Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2

Wenjing Pang1,5#, Weiyan Yao2#, Xin Dai2#, Aisen Zhang3,4, Lidan Hou1,5, Lei Wang1,5, Yu Wang1,5, Xin Huang1,5, Xiangjun Meng1,5✉, Lei Li1,5✉

1. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine affiliating Shanghai 9th People's Hospital, Shanghai, China.
2. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine affiliating Shanghai Ruijin Hospital, Shanghai, China.
3. Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical, Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
4. Department of Gerontology, Jiangsu People's Hospital affiliating to Nanjing Medical University, Nanjing, China.
5. Digestive Disease Research and Clinical Translation Center, Shanghai Jiaotong University, Shanghai, China.
#These authors contributed equally to the manuscript.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Pang W, Yao W, Dai X, Zhang A, Hou L, Wang L, Wang Y, Huang X, Meng X, Li L. Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2. Int J Biol Sci 2021; 17(13):3622-3633. doi:10.7150/ijbs.56271. Available from https://www.ijbs.com/v17p3622.htm

File import instruction

Abstract

Graphic abstract

New-onset diabetes mellitus has a rough correlation with pancreatic cancer (PaC), but the underlying mechanism remains unclear. This study aimed to explore the exosomal microRNAs and their potential role in PaC-induced β-cell dysfunction. The pancreatic β cells were treated with isolated exosomes from PaC cell lines, SW1990 and BxPC-3, before measuring the glucose-stimulated insulin secretion (GSIS), validating that SW1990 and BxPC-3 might disrupt GSIS of both β cell line MIN6 and primary mouse pancreatic islets. The difference in expression profiles between exosomes and exosome-free medium of PaC cell lines was further defined, revealing that miR-19a secreted by PaC cells might be an important signaling molecule in this process. Furthermore, adenylyl cyclase 1 (Adcy1) and exchange protein directly activated by cAMP 2 (Epac2) were verified as the direct targets of exogenous miR-19a, which was involved in insulin secretion. These results indicated that exosomes might be an important mediator in the pathogenesis of PaC-DM, and miR-19a might be the effector molecule. The findings shed light on the pathogenesis of PaC-DM.

Keywords: β cell dysfunction, miR-19a, exosome, pancreatic neoplasm