Hsa_circ_0054633 mediates apoptosis and insulin secretion in human pancreatic β cells through miR-409-3p/caspase-8 axis

Abstract

BackgroundCircRNAs are reported to be aberrantly expressed and perform biological functions in diverse processes. This study aimed to investigate the potential involvement of hsa_circ_0054633 in high glucose (HG)‑induced diabetic model and its potential mechanism. MethodsThe expression of hsa_circ_0054633, miR-409-3p and caspase-8 was detected by real-time PCR and western blotting. Cell viability, apoptosis and the protein levels of apoptosis-related factors were revealed by CCK-8 colorimetry, flow cytometry and western blotting, respectively. Insulin secretion was determined by enzyme-linked immunosorbent assay (ELISA) and the measurement of insulin-related transcription factors. The target association between miR-409-3p and hsa_circ_0054633 or caspase-8 was confirmed by dual-luciferase reporter assays and biotin-based pulldown assay. ResultsHsa_circ_0054633 was highly expressed and the expression of miR-409-3p was downregulated in serum of DM patients and HG-treated human pancreatic β cell line NES2Y. Further investigation indicated that hsa_circ_0054633 suppression promoted cell proliferation, inhibited apoptosis and facilitated insulin secretion in HG-treated NES2Y cells. Mechanical analysis revealed that hsa_circ_0054633 regulated caspase-8 expression via sponging miR-409-3p. Rescue experiments demonstrated that miR-409-3p knockdown or caspase-8 overexpression reversed the effects of hsa_circ_0054633 in HG-stimulated NES2Y cells. ConclusionInhibition of hsa_circ_0054633 protected against HG-induced NES2Y cell apoptosis and impairment of insulin secretion by regulating miR-409-3p/caspase-8 axis.