2. Academic Validation
  3. MicroRNA-7a inhibits Isl1 expression to regulate insulin secretion by targeting Raf1 and Mapkap1 in NIT-1 cells

MicroRNA-7a inhibits Isl1 expression to regulate insulin secretion by targeting Raf1 and Mapkap1 in NIT-1 cells

  • In Vitro Cell Dev Biol Anim. 2021 Sep;57(8):817-824. doi: 10.1007/s11626-021-00611-4.
Hui Liu  # 1 2,  Di Zhang  # 1 2 3,  Yewen Zhou 1,  Sheng Cui 4 5 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China.
  • 2 Institute of Reproduction and Metabolism, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China.
  • 3 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of China.
  • 4 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China. cuisheng@yzu.edu.cn.
  • 5 Institute of Reproduction and Metabolism, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China. cuisheng@yzu.edu.cn.
  • 6 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People's Republic of China. cuisheng@yzu.edu.cn.
  • # Contributed equally.
PMID: 34713362 DOI: 10.1007/s11626-021-00611-4
Abstract

Both microRNA-7a (miR-7a) and LIM-homeodomain transcription factor ISL1 are important factors regulating Insulin transcription and secretion, but the functional relationship and the interacting mechanisms between miR-7a and ISL1 in pancreatic islet β-cells remain unknown. The aims of this study were thus to identify the potential interactions and signaling communication between miR-7a and ISL1 in regulating Insulin transcription and secretion in the cultured NIT-1 cells. The results show that miR-7a inhibitor upregulates Isl-1 and Insulin gene expressions, and the Insulin secretion. Whereas miR-7a mimics inhibit ISL1 and Insulin gene expressions, and decreases the Insulin secretion. Furthermore, we identified the target gene of miR-7a using dual-luciferase reporter assay, and the results demonstrate that Raf1 and Mapkap1 is a direct target gene of miR-7a, modeling RAF1/MEK/ERK1/2 and mTORC2/Akt signaling pathway to regulate Isl1 expression, and thus influencing Insulin expression and secretion. Our results indicate that therapeutic inhibition of miR-7a function could be of relevance for preserving the function of pancreatic β-cells during the course of diabetes development, implicating miR-7, ISL1, and/or the connecting molecules may act as novel targets for pharmacological or gene therapy in diabetes and related Metabolic Disease, although much detailed studies are required in the further study.

Keywords

ISL1; Insulin; Mapkap1; Raf1; miR-7a.

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