2. Academic Validation
  3. circPRKAA1 activates a Ku80/Ku70/SREBP-1 axis driving de novo fatty acid synthesis in cancer cells

circPRKAA1 activates a Ku80/Ku70/SREBP-1 axis driving de novo fatty acid synthesis in cancer cells

  • Cell Rep. 2022 Nov 22;41(8):111707. doi: 10.1016/j.celrep.2022.111707.
Qidong Li 1,  Hanhui Yao 1,  Yichun Wang 1,  Yang Wu 1,  Rick F Thorne 2,  Youming Zhu 3,  Mian Wu 4,  Lianxin Liu 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China.
  • 2 Translational Research Institute, Henan Provincial and Zhengzhou City Key Laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People's Hospital, Academy of Medical Sciences, Zhengzhou University, Henan 450053, China.
  • 3 Department of Dental Implant Center, Stomatologic Hospital and College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei 230032, China. Electronic address: zym88888@mail.ustc.edu.cn.
  • 4 Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Translational Research Institute, Henan Provincial and Zhengzhou City Key Laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People's Hospital, Academy of Medical Sciences, Zhengzhou University, Henan 450053, China; Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China. Electronic address: wumian@ustc.edu.cn.
  • 5 Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China. Electronic address: liulx@ustc.edu.cn.
PMID: 36417875 DOI: 10.1016/j.celrep.2022.111707
Abstract

Many metabolism-related genes undergo alternative splicing to generate circular RNAs, but their functions remain poorly understood. Here we report that circPRKAA1, a circular RNA (circRNA) derived from the α1 subunit of AMP-activated protein kinase (AMPK), fulfills a fundamental role in maintaining lipid homeostasis. circPRKAA1 expression facilitates fatty acid synthesis and promotes lipid storage through two coordinated functions. First, circPRKAA1 promotes a tetrameric complex between the Ku80/Ku70 heterodimer and the mature form of sterol regulatory element-binding protein 1 (mSREBP-1) to enhance the stability of mSREBP-1. Second, circPRKAA1 selectively binds to the promoters of the ACC1, ACLY, SCD1, and FASN genes to recruit mSREBP-1, upregulating their transcription and increasing fatty acid synthesis to promote Cancer growth. circPRKAA1 biogenesis is negatively regulated by AMPK activity, with lower AMPK activation in hepatocellular carcinoma tissue frequently associated with elevated circPRKAA1 expression. This work identifies circPRKAA1 as an integral element of AMPK-regulated reprogramming of lipid metabolism in Cancer cells.

Keywords

AMPK; CP: Cancer; CP: Metabolism; Ku80/Ku70; SREBP-1; SRSF1; circPRKAA1; fatty acid synthesis.

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