Abstract 5471: LSD1 stimulates cell survival and epigenetic homeostasis via snail in hepatocellular carcinoma

Abstract

Abstract HCC is the fifth most common malignancy in the world. HCC generally arises in the context of chronic liver diseases, or other metabolic, dietary or toxic factors. Hypoxia is a critical microenvironment in hepatcarcinogenesis. It occurs in series of distinct steps that include tumor cell invasion and proliferation. The process of EMT required for liver cancer cell invasion is regulated by a family of E-box-binding transcription repressors, which include Snail and Slug. Protein N, the first discovered histone methylase, is an epigenetic enzyme playing important role in regulation of gene expression and function by removing mono- or dimethyl moieties from H3K4 and H3K9. However, the molecular mechanisms underlying these biological behaviors have not been completely elucidated. Here, we present the first evidence that expression of Protein N was transcriptionally induced by Hif1 under hypoxia condition. We also showed that the up-regulated Protein N enhanced HCC cell survival and sustained epigenetic homeostasis via activating Snail under hypoxic conditions in vitro/in vivo. Furthermore, we revealed that Protein N/Snail stimulated Hif1 expression by a positive feedback loop. Conclusively, we elicited that Protein N is an essential mediator in epigenetic aberrances of HCC (This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF-2016R1D1A1B03933763)). Note: This abstract was not presented at the meeting. Citation Format: Yong Hwa Jo, Minh Nam Nguyen, Tae Gyu Choi, Sung Soo Kim. LSD1 stimulates cell survival and epigenetic homeostasis via snail in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5471. doi:10.1158/1538-7445.AM2017-5471