LAUSR

Long non-coding RNAs (lncRNAs), encoding noncoding transcripts greater than 200 nucleotides, are multifunctional regulator of gene expression and play vital roles in various biological processes. Urothelial cancer-associated 1 (UCA1) is one such molecule and found to be dysregulated in the development of several cancer types, including those in bladder, colon, stomach, lung and breast. One previous study showed that an upregulation of UCA1 expression profile in hypopharyngeal cancer tissues relative to their adjacent normal counterparts significantly negated overall survival among these cancer patients. However, the molecular mechanism whereby UCA1 played any role in HPC, a subtype of head and neck cancer and often detected in advanced stages, remains elusive. In this report, we showed that ectopic UCA1 expression promoted cell migration and invasion while reducing cell proliferation. The increase of migration and invasion was accompanied by partial epithelial mesenchymal transition. By contrast, UCA1 depletion had the opposite effect. In addition to the presence of UCA1 in the culture medium (CM) and a stimulatory effect of CM derived from UCA1-OE cells on cell migration and invasion, we found a predominant nuclear localization of UCA1 in HPC cells. PTBP3, a RNA-binding protein, was identified as a novel interacting partner of UCA1 by RNA pulldown and mass spectrometry. PTBP3 silencing significantly reduced UCA1 mRNA expression, suggesting a regulatory role in UCA1 stability. While mapping the interacting domains between UCA1 and PTBP3, we are also in the process of identifying the involvement of UCA1-PTBP3 axis in hypopharyngeal carcinogenesis. We hope to validate if UCA1 can serve as a novel therapeutic target against or diagnostic marker for hypopharyngeal cancer. Citation Format: Li-Wha Wu. The cell- and non-cell autonomous actions of UCA1 dysregulation in hypopharyngeal cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3754.