1. Upregulation of Superenhancer‐Driven LncRNA FASRL by USF1 Promotes De Novo Fatty Acid Biosynthesis to Exacerbate Hepatocellular Carcinoma.
- Author
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Peng, Jiang‐Yun, Cai, Dian‐Kui, Zeng, Ren‐Li, Zhang, Chao‐Yang, Li, Guan‐Cheng, Chen, Si‐Fan, Yuan, Xiao‐Qing, and Peng, Li
- Subjects
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ACETYLCOENZYME A , *FATTY acids , *HEPATOCELLULAR carcinoma , *LINCRNA , *ACETYL-CoA carboxylase , *BIOSYNTHESIS - Abstract
Superenhancers drive abnormal gene expression in tumors and promote malignancy. However, the relationship between superenhancer‐associated long noncoding RNA (lncRNA) and abnormal metabolism is unknown. This study identifies a novel lncRNA, fatty acid synthesis‐related lncRNA (FASRL), whose expression is driven by upstream stimulatory factor 1 (USF1) through its superenhancer. FASRL promotes hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Furthermore, FASRL binds to acetyl‐CoA carboxylase 1 (ACACA), a fatty acid synthesis rate‐limiting enzyme, increasing fatty acid synthesis via the fatty acid metabolism pathway. Moreover, the expression of FASRL, USF1, and ACACA is increased, and their high expression indicates a worse prognosis in HCC patients. In summary, USF1 drives FASRL transcription via a superenhancer. FASRL binding to ACACA increases fatty acid synthesis and lipid accumulation to mechanistically exacerbate HCC. FASRL may serve as a novel prognostic marker and treatment target in HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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