12High Expression of N-acetyl transferase 9 in Cholangiocarcinoma and its Possible Role in Tumor Progression
Tamara Hoteit, Harlan P Jones, Pankaj ChaudharyAbstract
Background
Cholangiocarcinoma (CCA) is a rare and aggressive subtype of liver cancer known for its limited number of biomarkers, poor therapeutic options, and its resistance to anticancer drugs, which leads to difficulty in its early detection and its treatment. Thus, identifying new molecular targets for CCA is crucial. 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 N-acetyl transferases (NATs), which are involved in various functions, such as membrane targeting, protein stability, 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 expression and role in CCA have not been studied.
Methods
In this study, we aimed to assess NAT9’s expression and function in CCA. The Cancer Genome Atlas (TCGA) database was used to assess NAT9’s expression in normal and CCA patient tissue samples. NAT9’s expression was evaluated in normal and CCA patient tissue samples and cells lines using qRT-PCR and immunoblotting. NAT9 was then knocked down in cell lines showing high NAT9 expression, after which functional assays were performed. Cellular proliferation, migration, and invasion were assessed through MTT assays, scratch assays, Boyden chamber assays, and 3D-spheroid invasion assays.
Results
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. In cell lines and patient tissue samples, NAT9 was also overexpressed in the cancer samples compared to their normal and non-cancerous counterparts at both RNA and protein levels. In vitro, knocking down NAT9 revealed that NAT9 plays a role in CCA cellular proliferation, migration, and invasion.
Conclusion
These findings suggest that NAT9 plays a critical role in the aggressiveness and progression of cholangiocarcinoma.