2. Academic Validation
  3. Upregulation of Superenhancer-Driven LncRNA FASRL by USF1 Promotes De Novo Fatty Acid Biosynthesis to Exacerbate Hepatocellular Carcinoma

Upregulation of Superenhancer-Driven LncRNA FASRL by USF1 Promotes De Novo Fatty Acid Biosynthesis to Exacerbate Hepatocellular Carcinoma

  • Adv Sci (Weinh). 2022 Oct 28;e2204711. doi: 10.1002/advs.202204711.
Jiang-Yun Peng 1 2,  Dian-Kui Cai 3,  Ren-Li Zeng 4,  Chao-Yang Zhang 5,  Guan-Cheng Li 6 7,  Si-Fan Chen 1 2,  Xiao-Qing Yuan 1 8,  Li Peng 1 2
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, P. R. China.
  • 2 Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, P. R. China.
  • 3 Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, P. R. China.
  • 4 Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, P. R. China.
  • 5 Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • 6 Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Central South University, Changsha, 410078, P. R. China.
  • 7 Cancer Research Institute, Central South University, Changsha, 410078, P. R. China.
  • 8 Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, P. R. China.
PMID: 36307901 DOI: 10.1002/advs.202204711
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.

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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