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CLINICAL RESEARCH
Pyruvate kinase M2 plays a pivotal role in promoting PD-L1 expression and malignant behaviors of hepatoma cells
1
Key Laboratory of Tropical Translational Medicine, Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou, Hainan Province, China
2
Department of Medical Oncology, Second Affiliated Hospital, Hainan Medical University, Haikou, Hainan Province, China
These authors had equal contribution to this work
Submission date: 2025-01-21
Final revision date: 2025-07-09
Acceptance date: 2025-07-14
Online publication date: 2025-08-23
Corresponding author
Mingyue Zhu
Key Laboratory of Tropical Translational Medicine Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical University 3 Xueyuan Road Longhua District Hainan Medical University Haikou 571199 Hainan, China
Key Laboratory of Tropical Translational Medicine Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical University 3 Xueyuan Road Longhua District Hainan Medical University Haikou 571199 Hainan, China
Mengsen Li
Key Laboratory of Tropical Translational Medicine Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical University 3 Xueyuan Road Longhua District Hainan Medical University Haikou 571199 Hainan, China
Key Laboratory of Tropical Translational Medicine Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical University 3 Xueyuan Road Longhua District Hainan Medical University Haikou 571199 Hainan, China
KEYWORDS
pyruvate kinase M2hepatocellular carcinomaWarburg effectPD-L1malignant behaviorsPI3K/Akt signaling pathway
TOPICS
ABSTRACT
Introduction:
Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme that regulates glucose metabolic reprogramming (Warburg effect), but the correlation between PKM2 and PD-L1 or malignant behaviors in hepatocellular carcinoma (HCC) cells remains unknown. This study explored the role of PKM2 and the Warburg effect on the expression of PD-L1 and the malignant behaviors of HCC cells.
Material and methods:
The relationship between the Warburg effect and key enzymes and signaling pathways was analyzed using bioinformatics; the expression of PD-L1, PKM2, and hexokinase 2 (HK2) in 30 patients’ HCC tissues and paired para-cancerous tissues was detected by immunohistochemistry and Western blotting. Short hairpin RNA (shRNA) silencing the expression of PKM2 was used to explore its influence on the expression of PD-L1 in HCC cells. The malignant behaviors of HCC cells were detected by scratch test, plate cloning experiment, Transwell migration experiment, and EdU staining; the concentrations of lactic acid, pyruvate, and ATP and the consumption of glucose were detected using a reagent kit.
Results:
Biological information database and detection of HCC tissues and paired para-cancerous tissues showed that the expression levels of PKM2 and PD-L1 were significantly higher in HCC tissues than in paired para-cancerous tissues, and the expression of PKM2 was positively correlated with PD-L1 expression. PKM2 could promote the proliferation and migration of HCC cells, and stimulate the expression of PD-L1 through activating the PI3K/Akt signaling pathway in HCC cells.
Conclusions:
PKM2 was able to upregulate the expression of PD-L1 and stimulate the malignant behaviors of HCC cells. Targeting PKM2 is a promising strategy for liver cancer treatment.
Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme that regulates glucose metabolic reprogramming (Warburg effect), but the correlation between PKM2 and PD-L1 or malignant behaviors in hepatocellular carcinoma (HCC) cells remains unknown. This study explored the role of PKM2 and the Warburg effect on the expression of PD-L1 and the malignant behaviors of HCC cells.
Material and methods:
The relationship between the Warburg effect and key enzymes and signaling pathways was analyzed using bioinformatics; the expression of PD-L1, PKM2, and hexokinase 2 (HK2) in 30 patients’ HCC tissues and paired para-cancerous tissues was detected by immunohistochemistry and Western blotting. Short hairpin RNA (shRNA) silencing the expression of PKM2 was used to explore its influence on the expression of PD-L1 in HCC cells. The malignant behaviors of HCC cells were detected by scratch test, plate cloning experiment, Transwell migration experiment, and EdU staining; the concentrations of lactic acid, pyruvate, and ATP and the consumption of glucose were detected using a reagent kit.
Results:
Biological information database and detection of HCC tissues and paired para-cancerous tissues showed that the expression levels of PKM2 and PD-L1 were significantly higher in HCC tissues than in paired para-cancerous tissues, and the expression of PKM2 was positively correlated with PD-L1 expression. PKM2 could promote the proliferation and migration of HCC cells, and stimulate the expression of PD-L1 through activating the PI3K/Akt signaling pathway in HCC cells.
Conclusions:
PKM2 was able to upregulate the expression of PD-L1 and stimulate the malignant behaviors of HCC cells. Targeting PKM2 is a promising strategy for liver cancer treatment.
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