Abstract 6724: The role of human leukocyte antigen F adjacent transcript 10 in the tumorigenesis of nasopharyngeal carcinoma

Abstract Nasopharyngeal carcinoma (NPC) is a highly aggressive malignancy prevalent in Southern China and Southeast Asia related to Epstein-Barr virus (EBV) infection and genetic variations at the Human Leukocyte Antigen (HLA) locus. Human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10) is a ubiquitin-like protein modifier that can modulate its substrates by (1) mediating degradation via the 26S proteasome or (2) altering function through Fat10ylation. Previously studies have found FAT10 overexpression in various cancers, including gliomas and hepatocellular carcinoma, promoting tumorigenesis by altering cell proliferation, metastasis, and angiogenesis. Nevertheless, the precise role of FAT10 in NPC remains ambiguous. NPC public cohort GSE150430 showed high expression of FAT10 in NPC malignant cells. We also found overexpression of FAT10 in both NPC cell lines and patient-derived xenografts (PDXs) by real-time polymerase chain reaction (RT-PCR) and western blot at mRNA and protein level respectively. FAT10 overexpression in both NPC cell line C666-1 and immortalized normal nasopharyngeal cell line NP460 by lentiviral transduction increased proliferation proved by XTT assay, colony formation assay, and ki67 staining assay. Transwell migration and wound healing assay were performed in FAT10 overexpression cancer cell line and normal cell line to show the enhancement of migration ability. ROS production was also increased in these FAT10 overexpression cell lines by using the CellROX Green reagent. However, the western blot result showed that stemness ability cannot be changed in NP460. To conclude, our findings indicated that FAT10 may play a significant role in the tumorigenesis of NPC. Its underlying mechanism will be further explored. Citation Format: Yusi Liang, Ngar Woon Kam, Zhuoyou YU, Ho Fun LEE. The role of human leukocyte antigen F adjacent transcript 10 in the tumorigenesis of nasopharyngeal carcinoma [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 6724.