SNHG1-miR-186-5p-YY1 feedback loop alleviates hepatic ischemia/reperfusion injury

Abstract

ABSTRACT As a common cause of liver injury, hepatic ischemia/reperfusion injury (HIRI) happens in various clinical conditions including trauma, hepatectomy and liver transplantation. Since transcription factor Yin Yang 1 (YY1) was reported to be downregulated after ischemia/reperfusion (I/R) injury, we focused on YY1 to explore its function in HIRI by functional assays like Cell Counting Kit-8 (CCK-8) assays and flow cytometry assays. The RT-qPCR assay revealed that YY1 was downregulated in hepatocytes after I/R injury. The function assays disclosed that YY1 facilitated cell viability and proliferation, but hindered cell apoptosis in hepatocytes after I/R injury. Through mechanism assays including luciferase reporter assay, RIP and RNA pulldown assay, miR-186-5p was found to bind with YY1 and promote hepatocyte apoptosis by targeting YY1. Subsequently, we verified that small nucleolar RNA host gene 1 (SNHG1) could sponge miR-186-5p to upregulate YY1. Importantly, we figured out that YY1 had a positive regulation on SNHG1. Along the way, YY1 was identified as the upstream transcription factor for SNHG1. In conclusion, our study unveiled a novel competing endogenous RNA (ceRNA) pattern of SNHG1/miR-186-5p/YY1 positive feedback loop in hepatic I/R injury, which might provide new insight into prevention of HIRI during liver transplantation or hepatic surgery.