Abstract 6985: The oncogenic functions and action mechanism of UTP14A, a subunit required for 18S rRNA synthesis, in head and neck cancer

Abstract Head and neck cancer (HNC) is the sixth common malignancy in the world and > 90% of HNC cases are squamous cell carcinoma in origin. Oral cancer is one major HNC subtype. Despite the recent advancements in cancer diagnostics and therapeutics, the 5-yr survival rate of advanced HNC patients remains <50%. Ribosomes are the cellular factories responsible for making proteins. The hyper-activation of ribosome biogenesis initiated by oncogene gain or tumor suppressor gene loss plays a critical role in cancer initiation and progression. Ribosome biogenesis is a complex and energy intensive process that involves hundreds of factors. UTP14A gene encodes a member of the uridine triphosphate 14 family and is an essential component of a large ribonucleoprotein complex bound to the U3 small nucleolar RNA. Previous studies have demonstrated that UTP14A plays a key role in the synthesis of ribosomes and 18S rRNA, and is overexpressed in several malignancies. However, the biological functions and underlying mechanisms of UTP14A in HNC remain elusive. We found not only the increase of UTP14A mRNA expression in TCGA-HNC database but also its negative impact on patient clinical outcome. UTP14A depletion significantly impaired HNC cell proliferation, migration and invasion in vitro. Ectopic overexpression had the opposite effect, suggesting an oncogenic role for UTP14A in HNC. Through gene set enrichment analysis of pairwise RNA sequencing results, several genes involved in the process of epithelial mesenchymal transition (EMT) were potentially associated with manipulated UTP14A expression. We also detected a concordant change of lipid droplet numbers and its surface marker expression in UTP14A-manipulated cells, respectively, by BODIPY staining and immunhistochemical staining. Western blot analysis validated a positive relationship of EMT markers and COX-2, a potential mediator of lipid metabolism and EMT, with altered UTP14A expression. The involvement of COX2 in UTP14A mediation was confirmed by using both pharmacological inhibition and genetic manipulation. We also identified p38 as a central downstream effector but acting upstream from COX-2 in UTP14A mediation in oral cancer cells. We believe that our study of UTP14A-mediated oncogenic signaling axis can potentially be harnessed as a novel therapeutic target against HNC although more mechanistic studies may be needed. Citation Format: Li-Wha Wu, Chen-Ni Chang, Pulak K. Biswas, Sen-Tien Tsai. The oncogenic functions and action mechanism of UTP14A, a subunit required for 18S rRNA synthesis, in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6985.