Objective To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha (PPP2R3A) and hexokinase 1 (HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.

JIAO Ning;JI Wan Sheng;ZHANG Biao;SHANG Yu Kui;ZHANG Yu Chen;YU Wei Qun;JIN Hai Long;LI Chao;ZHANG Cheng Ying;YAN Cheng;YUE Wen;ZHANG Qing

Weifang Medical university,Weifang 261053,Shandong,China;Department of Organ Transplantation,The Third Medical Center of PLA General Hospital,Beijing 100039,China;Clinical Research Center,Affiliated Hospital of Weifang Medical University,Weifang 261042,Shandong,China;Stem Cell and Regenerative Medicine Lab,Institute of Health Service and Transfusion Medicine,Beijing 100850,China;Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing 100083,China;Senior Department of Ophthalmology,The Third Medical Center of PLA General Hospital,Beijing 100039,China;Department of General Practice,The Third Medical Center of PLA General Hospital,Beijing 100039,China

生物医学与环境科学（英文版）

[1]JIAO Ning;JI Wan Sheng;ZHANG Biao;SHANG Yu Kui;ZHANG Yu Chen;YU Wei Qun;JIN Hai Long;LI Chao;ZHANG Cheng Ying;YAN Cheng;YUE Wen;ZHANG Qing-.Overexpression of Protein Phosphatase 2 Regulatory Subunit B"Alpha Promotes Glycolysis by Regulating Hexokinase 1 in Hepatocellular Carcinoma)[J].生物医学与环境科学（英文版）,2022(07):622-632

PPP2R3A

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