Abstract 2642: High expression of N-acetyl transferase 9 in cholangiocarcinoma and its possible role in tumor progression

Abstract Cholangiocarcinoma (CCA) is a rare and aggressive subtype of liver cancer known for its limited number of biomarkers and its resistance to anticancer drugs, leading to difficulty in its early detection. The five-year survival rate for CCA varies between 2% and 24%, depending on factors such as the severity of the cancer, the presence of metastasis, and the timing of diagnosis. Currently, surgery is the most effective treatment option, but only under certain criteria, such as early cancer detection and absence of metastasis. N-terminal acetylation is an epigenetic modification that plays an important role in the regulation of cellular growth and function. This process is modulated by the enzyme N-acetyl transferase (NAT), which is involved in various functions, such as protein stability, membrane targeting, gene silencing, and drug resistance. These functions can regulate cell cycle progression, cell proliferation, and energy metabolism, all of which are key characteristics of cancer. NAT9, a subset of NATs, has abundant transcripts in breast, ovarian, and endometrial cancers; however, its role and expression in CCA have not been studied. In this study, we aimed to assess the expression, role, and function of NAT9 in CCA progression and metastasis using cell lines and patient tissue samples. According to The Cancer Genome Atlas (TCGA) database, NAT9 is overexpressed in patients with CCA, and its expression increases with the increase in the grade of CCA. NAT9 was also overexpressed in CCA cell lines and patient tissue samples compared to their normal and non-cancerous counterparts at both RNA and protein levels. In vitro, NAT9 knockdown experiments showed that NAT9 plays a role in CCA cellular proliferation and migration. These findings suggest that NAT9 plays a critical role in the development and progression of CCA. Citation Format: Tamara Hoteit, Harlan P. Jones, Pankaj Chaudhary. High expression of N-acetyl transferase 9 in cholangiocarcinoma and its possible role in tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2642.