Abstract 1515: NCOA3 promotes tumor growth by activating telomerase reverse transcriptase and predicts poor prognosis in hepatocellular carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer death worldwide. The rising incidence and mortality rate of HCC in most countries are due to an increased rate of chronic Hepatitis C virus infection, alcohol abuse and obesity. The molecular mechanisms leading to the development of HCC are complicated, consist of various genetic and epigenetic changes, and are associated with altered signaling pathways. Among these molecular events, elevated expression of human telomerase reverse transcriptase (TERT) is an important alteration in HCC and a hallmark of human cancers. TERT is highly expressed in HCC and positively correlated with the development of HCC. However, the detailed mechanism of TERT activation in HCC remains largely unclear. Here, we identified nuclear receptor coactivator-3 (NCOA3) as a TERT promoter-binding protein, which specifically bound to the -234~-144 region of the TERT promoter. Overexpression of NCOA3 enhanced TERT promoter activity and expression, and promoted HCC cell growth. Moreover, we demonstrated that NCOA3 interacted with the transcription factor SP1 to promote TERT expression. The clinical data showed that the expression of NCOA3 and TERT were positively correlated and elevated in HCC tissues, and HCC patients with high level of NCOA3/TERT had poor prognosis. Collectively, our study revealed that NCOA3 bound to the TERT promoter and activated TERT expression to promote HCC growth, indicating that the NCOA3/TERT signaling pathway could be a potential therapeutic target for HCC. [Funding support: This work was supported by the funds from the National Natural Science Foundation of China (81772925, 81472178, 81702761), the State “973 Program” of China (2014CB542005), and the Natural Science Foundation of Guangdong Province (2016A03031100, 2015A030313018, 2017A030313615)]. Citation Format: Miao Chen, Wenbin Li, Yixin Li, Changlin Zhang, Ge Qin, Qian Long, Dingbo Shi, Wei Guo, Shuihan Shi, Kefang Zhang, Wuguo Deng. NCOA3 promotes tumor growth by activating telomerase reverse transcriptase and predicts poor prognosis in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1515.