Abstract 3504: ARS2 and paraspeckle interactions: A nexus for lncRNA mediated drug resistance and cancer progression in hepatocellular carcinoma

Abstract Paraspeckles, elaborate sub-nuclear assemblies composed of the lncRNA NEAT1-2 and a cohort of RNA-binding proteins, have a noted association with cancer progression and drug resistance. The specific mechanisms, however, have remained obscure. Our investigation into Hepatocellular Carcinoma (HCC) reveals a critical interaction: the sequestration of ARS2—an RNA-binding protein vital for the suppression of mRNA transcripts and the maturation of miRNAs—within paraspeckles. This sequestration leads to increased levels of NEAT1-2, derails miRNA processing, and diminishes the gene-silencing function of ARS2, thereby enhancing the expression of oncogenic genes. This discovery positions the ARS2-paraspeckle axis as a pivotal factor in cancer biology and a promising target for future treatments. Citation Format: Gobi Thillainadesan, Hon Sing Leong, Omar Alawamry. ARS2 and paraspeckle interactions: A nexus for lncRNA mediated drug resistance and cancer progression in hepatocellular carcinoma [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 3504.