Overexpression of Protein Phosphatase 2 Regulatory Subunit B

Ning Jiao; Wan Sheng JI; Biao Zhang; Yu Kui Shang; Yu Chen Zhang; Wei Qun YU; Hai Long Jin; Chao LI; Cheng Ying Zhang; Cheng Yan; Wen Yue; Qing Zhang

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Overexpression of Protein Phosphatase 2 Regulatory Subunit B"Alpha Promotes Glycolysis by Regulating Hexokinase 1 in Hepatocellular Carcinoma.

Author: Ning JIAO ^{1
,

2} ; Wan Sheng JI ³ ; Biao ZHANG ⁴ ; Yu Kui SHANG ⁵ ; Yu Chen ZHANG ⁴ ; Wei Qun YU ⁶ ; Hai Long JIN ² ; Chao LI ² ; Cheng Ying ZHANG ⁷ ; Cheng YAN ^{1
,

2} ; Wen YUE ⁴ ; Qing ZHANG ²
Author Information

1. Weifang Medical university, Weifang 261053, Shandong, China
2. Department of Organ Transplantation, The Third Medical Center of PLA General Hospital, Beijing 100039, China.
3. Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang 261042, Shandong, China.
4. Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China.
5. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100083, China.
6. Senior Department of Ophthalmology, The Third Medical Center of PLA General Hospital, Beijing 100039, China.
7. Department of General Practice, The Third Medical Center of PLA General Hospital, Beijing 100039, China.
Publication Type:Journal Article
Keywords: Glycolysis; Hepatocellular carcinoma; Hexokinase 1; PPP2R3A
MeSH: Carcinoma, Hepatocellular/pathology*; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glycolysis; Hexokinase/metabolism*; Humans; Liver Neoplasms/pathology*; Protein Phosphatase 2/metabolism*; RNA, Small Interfering/metabolism*
From: Biomedical and Environmental Sciences 2022;35(7):622-632
CountryChina
Language:English
Abstract: 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.