circSMAD6 upregulation by Hnrnpa2b1-dependent m6A modification promotes aerobic glycolysis and metastasis of hepatocellular carcinoma cells by regulating Mir-30d-3p/CNPY2 axis
The role of circSMAD6 in hepatocellular carcinoma
image: Deputy Chief Physician of Sichuan Provincial People's Hospital
Credit: Immunity & Inflammation
Hepatocellular carcinoma (HCC) is one of the most frequent digestive malignancies and constitutes the second leading cause of cancer-associated death in China. Despite the development of immunotherapies and targeted therapies, the prognosis of patients with HCC remains unsatisfactory, ascribed to the widespread metastases. The molecular mechanisms underlying HCC metastasis remain elusive. Therefore, it is indispensable to identify metastasis-related markers and develop targeted therapies for HCC. We herein found that circSMAD6 was an m6A target of hnRNPA2B1, which increased the m6A levels of circSMAD6 as well as its mRNA levels. Ectopic expression of circSMAD6 accelerated glucose uptake, lactate production, hepatic tumorigenesis and metastasis in vitro and in vivo, whereas knockdown of circSMAD6 produced the contrary effects. Moreover, circSMAD6 interacted with miR-30d-3p and acted as its sponge to activate CNPY2/AKT signaling, contributing to the progression of HCC cells. Our findings demonstrate that circSMAD6 upregulation by hnRNPA2B1-dependent m6A-modification promotes aerobic glycolysis and metastasis of HCC cells by regulating miR-30d-3p/CNPY2 axis.
Reference
Title of original paper: CircSMAD6 upregulation by hnRNPA2B1-dependent m6A modification promotes aerobic glycolysis and metastasis of hepatocellular carcinoma cells by regulating miR-30d-3p/CNPY2 axis
Journal: Chinese Medical Journal
DOI:https://doi.org/10.1097/CM9.0000000000004171
About University of Electronic Science and Technology
Website: https://www.uestc.edu.cn/
About Dr. Guangpeng Zhou from University of Electronic Science and Technology
Dr. Guangpeng Zhou is Deputy Chief Physician at Sichuan Provincial People's Hospital and Associate Researcher at the University of Electronic Science and Technology of China. He is a Reserve Candidate for Academic and Technical Leaders of Sichuan Provincial Health Commission. Dr. Zhou is a member of the hyperuricemia and gout group of the Endocrine and Metabolic Disease Branch of the Chinese Medical Doctor Association, the Standing Committee of Chronic Disease Prevention and Education of the Chinese Medical Education Association, and the Peripheral Vascular Disease Management Branch of Chinese Geriatrics Association. He serves in diabetes and obesity organizations in Sichuan.
Funding information
Our work was supported by the grants from Natural Science Foundation of Shanghai (No. 21ZR1448700), National Natural Science Foundation of China (No. 82074161, 81873143). and Shanghai Science and Technology Innovation Plan Star Cultivation (Sailing Special Project, No. 22YF1432600).