Abstract 349: LncRNA Myca controls hepatocellular carcinoma growth and progression

Abstract

Abstract Long non-coding RNAs (lncRNAs) have been shown to play critical roles in the tumorigenesis and progression of cancer. From a clinic and genomic perspective of evidence, the MYC signaling plays a crucial role in triggering hepatocellular carcinoma (HCC) and therefore represents an attractive target for HCC intervention. However, no specific drug is currently available to target MYC directly due to the lack of an enzymatic pocket. Therefore, deciphering the critical lncRNAs that functionally crosstalk with MYC protein levels may offer novel therapeutic strategies in HCC. Here we identify the involvement of a lncRNA Myca (Myc Activator) in HCC through controlling MYC protein levels. Overexpression of Myca triggers tumor growth in a MYC-dependent manner, while inactivation of Myca by antisense oligonucleotides (ASOs) profoundly reduces MYC protein levels, thus suppressing tumor progression in vitro. Mechanistically, we show that Myca attenuates MYC ubiquitination and leads to MYC accumulation. Clinically, overexpression of Myca is positively correlated with Hi-MYC transcriptional profile and HCC progression from the TCGA dataset. Together, our findings not only identify Myca in controlling MYC protein levels but also provide Myca as a new therapeutic lncRNA target for the HCC intervention. Citation Format: Hsin-Yi Chen, Yu-Yun Weng, Wei-Chien Yuan, Yu-Ru Lee. LncRNA Myca controls hepatocellular carcinoma growth and progression [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 349.