The PLCG2 Inhibits Tumor Progression and Mediates Angiogenesis by VEGF Signaling Pathway in Clear Cell Renal Cell Carcinoma
Open accessAbstract
Background: Clear cell renal cell carcinoma (ccRCC) represents the most prevalent form of renal cell carcinoma. The management of early-stage ccRCC has a better prognosis, while patients with metastatic ccRCC have a lower five-year survival rate. Angiogenesis serves as the fundamental process underlying tumor metastasis. Therefore, it is crucial to discover new targets for angiogenesis to improve patient survival rates. Methods: The Cancer Genome Atlas database, International Cancer Genome Consortium database, Clinical Proteomic Tumor Analysis Consortium database, and a gene set of the vascular endothelial growth factor (VEGF) signaling pathway were utilized to identify differentially expressed genes. Western blot (WB), quantitative real-time polymerase chain reaction, and immunohistochemistry were employed to validate the downregulation of phospholipase C gamma 2 (PLCG2) in ccRCC tissues and cells. Cell Counting Kit-8 (CCK-8) assays, transwell assays, tube formation assays, and oil-red staining were performed to elucidate the biological functions of PLCG2 in tumor cells. Gene set enrichment analysis was applied to explore the downstream pathway. Subcutaneous tumor models and live small animal fluorescent imaging assay were utilized for in vivo investigation of the roles played by PLCG2. Results: Our study has identified a novel biomarker, PLCG2, for ccRCC. PLCG2 is a central gene in regulating angiogenesis in ccRCC, as validated by bioinformatics analysis. The findings revealed a diminished expression of PLCG2 in both ccRCC tissues and cells. Further experiments in vivo and in vitro have demonstrated the significant roles of PLCG2 in tumor proliferation, invasion, migration, and lipid accumulation. Results of tube formation assays and WB support the role of PLCG2 in regulating VEGFA expression and angiogenesis. Conclusions: Our results show that PLCG2 functions as a potential biomarker and an independent prognostic indicator for ccRCC. PLCG2 may modulate angiogenesis by influencing the expression of VEGFA. Therefore, targeting PLCG2 could potentially lead to drug discovery and improved cancer treatment strategies.
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Prior studies have shown contradictory findings with respect to the role of PLCG2 in proliferation and apoptosis.
“Prior studies have shown contradictory findings with respect to the role of PLCG2 in proliferation and apoptosis.”
From Alzheimer's disease–associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell–derived microglia‐like cells (2025) · cites this paper as [49]
The Conclusions (section 5; page unavailable) report that PLCG2 inhibits proliferation in clear cell renal cell carcinoma, but they do not describe contradictory findings from prior studies. Searches for conflicting findings and apoptosis found no passage addressing either point; the Discussion (section 4; page unavailable) discusses differing roles of MAPK components, not contradictory findings about PLCG2. (LLM, conf=0.74)
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- Authors
- Zhao, C., Miao, D., Tan, D., Shi, J., Lv, Q., Xiong, Z., & Zhang, X.
- Affiliations
- Wuhan Union Hospital (CN)
- Corresponding author
- Xiong, Zhiyong
- Zhang, Xiaoping
- Venue
- Frontiers in Bioscience-Landmark
- Publisher
- IMR Press
- Published
- 2024-11-20
- Volume
- 29
- Issue
- 11
- Pages
- 390-390
- ISSN
- 2768-6698 (ISSN-L)
- 2768-6701
- OpenAlex
- W4404755148
- Cited by
- 6
- References
- 6
- Citations by year
- 2026: 3 · 2025: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Bioscience-Landmark (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (82202911, 82300786)
- Hubei Provincial Natural Science Foundation Projects (2024AFB640)
- Wuhan Yingcai (02.05.22030029)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- PLCγ2, clear cell renal cell carcinoma, angiogenesis, VEGF pathway, VEGF-A, tumor progression, prognostic factors, metastasis, tumor cell migration and invasion, lipid accumulation
- MeSH terms
- Angiogenesis, Animals, Carcinoma, Renal Cell, Cell Movement, Female, Humans, Kidney Neoplasms, Male, Mice, Nude, Neovascularization, Pathologic, Signal Transduction, Gene Expression Regulation, Neoplastic, Disease Progression, Vascular Endothelial Growth Factor A, Cell Line, Tumor, Cell Proliferation, Mice, Phospholipase C gamma
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