Research Paper Volume 11, Issue 5 pp 1342—1355

MicroRNA-127 inhibits cell proliferation via targeting Kif3b in pancreatic β cells

Ziyang Shen 1, *, , Hemin Jiang 1, *, , Hsiang-Ting Hsu 1, *, , Li Qian 1, , Qi Fu 1, , Min Shen 1, , Shu Chen 1, , Tao Yang 1, ,

  • 1 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
* Equal contribution

received: August 14, 2018 ; accepted: February 17, 2019 ; published: March 1, 2019 ;

https://doi.org/10.18632/aging.101835
How to Cite

Copyright: Shen et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

MicroRNAs (miRNAs) have been implicated in β cells dysfunction. Previous studies indicated that miR-127 was specifically abundant in β cells and one of its target genes, Kif3b, promoted cell proliferation. However, the impact of the miR-127-Kif3b axis on β cells remains unknown. In this study, we revealed that miR-127 level was declined both in islets from the mice with a high-fat diet and in MIN6 cells with elevated glucose treatment. The elevated level of miR-127 attenuated β cell proliferation by repressing Kif3b expression without affecting apoptosis and cell cycle, and it dampened insulin secretion. Moreover, β cell-derived miR-127 could also affect the islet endothelial cell-line, MS1, in vitro via the transfer of extracellular vesicles (EVs). Treating MS1 cells with the EVs secreted by MIN6 cells exhibited a higher ability in cell migration and tube formation. However, this effect was abolished by the miR-127 inhibitor co-cultured with EVs-treated MS1 cells. Thus, we define that miR-127 is a crucial regulator of insulin secretion and cell proliferation in pancreatic β cells as well as a potential functional regulation factor in islet endothelial cells.

Abbreviations

EVs: extracellular vesicles; HFD: high fat diet; NFD: normal fat diet; T2D: type 2 diabetes; miRNAs: MicroRNAs; NTA: nanoparticle tracking analysis; TEM: transmission electron microscopy; qRT-PCR: quantitative real-time PCR; GSIS: glucose stimulated insulin secretion; CCK-8: cell counting kit-8.