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.
Keywords: acetyl-CoA carboxylase 1; fatty acid synthesis; fatty acid synthesis-related long noncoding RNAs; hepatocellular carcinoma; lipid metabolism; long noncoding RNA; superenhancer.
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