Abstract
Abstract Long noncoding RNAs (lncRNAs) are major regulators of many cellular processes including cell cycle progression, cell proliferation and tumorigenesis. In this study, we identify a novel lncRNA, GTF2A1-AS1, and reveal its effects on cell cycle progression and cancer growth. Inhibition of GTF2A1-AS1 expression alters cell cycle distribution, leading to a decrease in the number of G1 cells and a concomitant increase in all other stages of the cell cycle, and in particular S phase, suggesting its involvement in the regulation of G1/S transition. Accordingly, knock down of GTF2A1-AS1 enhances G1 phase exit upon release from a late G1 block. In agreement with its suggested role in G1/S transition, prolonged silencing of GTF2A1-AS1 enhances proliferation of human cancer cells. GTF2A1-AS1 RNA is mostly nuclear and its gene is localized upstream to the protein-coding gene GTF2A1. GTF2A1-AS1 functions in trans to repress the expression of EIF5A2 and HOXA13. Knockdown of either EIF5A2 or HOXA13 rescues the effects of GTF2A1-AS1 silencing on cell proliferation, indicating that it functions mainly by modulating the levels of these two proteins. In agreement with the effect of GTF2A1-AS1 silencing on cell cycle progression and cell proliferation, low levels of GTF2A1-AS1 are associated with reduced survival in brain cancer patients. In conclusions, our data identify GTF2A1-AS1 as a novel lncRNA that regulates cell-cycle progression and cell proliferation and has a potential role in human cancer. Citation Format: Yael Goldstein, Tali Nizri-Megnaji, Doron Ginsberg. A novel lncRNA, GTF2A1-AS1, is required for cell cycle progression and cell proliferation. [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 3762.
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