Abstract 6011: RNA-seq analysis of liver from NASH derived HCC model mouse treated with streptozotocin-high fat diet

Abstract

Abstract Introduction; Non-alcoholic steatohepatitis (NASH) is a chronic liver disease often associated with type 2 diabetes. It sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). Therapeutic agents for NASH have not yet been developed, and an animal model with high clinical correlation is required. The STAM mouse is a NASH model mouse with a background of type 2 diabetes. This mouse model shows the same pathological progression as human NASH patients, and has been used for the evaluation of many drug candidates, as well as basic research. However the gene profile, including mutations, has not been elucidated in this model. In this study, we analyzed the RNA-seq data of STAM mice at each pathological stage and examined the clinical correlation at the gene level. Methods;NASH was induced in male mice by a single subcutaneous injection of 200 ug streptozotocin solution 2 days after birth and feeding with high fat diet after 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16 and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80°C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. Results: The gene expression of the canonical pathway in NASH progression from steatosis to hepatocellular carcinoma was analyzed. Increased expression was observed in CCL2, TLR4, HSP47, alpha-SMA, c-Myc, and cyclin D1. Since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. Citation Format: Taishi Hashiguchi, Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H Pigney. RNA-seq analysis of liver from NASH derived HCC model mouse treated with streptozotocin-high fat diet [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6011.