microRNA-375通过下调PSEN1的表达诱导胰岛β细胞凋亡

MicroRNA-375 Induces Islet IS-cells Apoptosis by Decreasing the Protein Level of PSEN1

目的研究miR-375能否诱导胰岛β细胞凋亡并对其机制进行初步探索。方法在大鼠胰岛β细胞系INS-1细胞中转染miR-375，运用流式细胞术检测INS-1细胞的凋亡情况。荧光素酶报告基因技术分析miR-375对Psenl的作用。Western印迹检测PSENl蛋白的表达。Hoechst染色检测干扰PSENl对INS-1细胞凋亡的影响。结果过表达miR-375诱导INS-1细胞凋亡；miR-375能够抑制Psenl基因3’UTR荧光素酶活性；过表达miR-375抑制PSENl蛋白的表达，干扰miR-375能够增加PSEN1蛋白的表达：干扰PSEN1的表达能够诱导INS-1细胞凋亡。结论miR-375通过下调PSENl的蛋白表达进而诱导胰岛β细胞凋亡。

Objective To investigate whether miR-375 could induce apoptosis of pancreatic beta-cells and its mechanism. Methods The miR-375 mimics were transfected into INS-1 cells and the apoptosis of INS-1 was detected by flow cytometry. Luciferase reporter gene assay was used to detect the effect of miR-375 on Psenl3＇UTR. The protein level of PSEN1 was detected by Western blotting. By Hoechst staining, the effect of PSEN1 on INS-1 apoptosis was examined. Results Overexpression miR-375 could induce INS-1 apoptosis. MiR-375 could directly suppress the Luciferase ac tivity of Psenl3＇UTR and decrease the protein levels. Interfering miR-375 could restore the expression of PSEN1. Silencing PSEN1 could induce apoptosis of INS-1. Conclusion miR-375 induces pancreatic β-cell apoptosis by decreasing the protein level of PSEN1.