Targeting the NCOA3-SP1-TERT axis for tumor growth in hepatocellular carcinoma

• DOI: 10.1038/s41419-020-03218-x
• Publication Date: 2020-11-25T12:03:43Z
• Authors: Wenbin Li; Yue Yan; Zongheng Zheng; Qiaohua Zhu; Qian Long; Silei Sui; Meihua Luo; Miao Chen; Yizhuo Li; Yijun Hua; Wuguo Deng; Renchun Lai; Liren Li
• Keywords: 0301 basic medicine; 0303 health sciences; Carcinoma, Hepatocellular; QH573-671; Liver Neoplasms; Mice, Nude; Oncogenes; Transfection; Survival Analysis; Article; 3. Good health; Nuclear Receptor Coactivator 3; Mice; 03 medical and health sciences; Biomarkers, Tumor; Animals; Humans; Female; Cytology

Hepatocellular carcinoma (HCC) has a high mortality rate and lacks an effective therapeutic target. Elevated expression of human telomerase reverse transcriptase (TERT) is important hallmark in cancers, but the mechanism by which TERT activated differentially cancers poorly understood. Here, we have identified nuclear receptor coactivator-3 (NCOA3) as new modulator tumor growth HCC. NACO3 specifically binds to promoter at -234 -144 region transcriptionally activates expression. NCOA3 promotes HCC cell progression vitro vivo through upregulating signaling. Knockdown suppresses viability colony formation, whereas overexpression rescues this suppression. interacts with recruits SP1 binding on promoter. also inhibits Wnt signaling-related genes no effect Notch signaling-targeting genes. Moreover, positively correlated tissues, both predicts poor prognosis patients. Our findings indicate that targeting NCOA3-SP1-TERT signaling axis may benefit