PLCγ2 通过 VEGF 信号通路抑制透明细胞肾细胞癌的肿瘤进展和血管生成。

The PLCG2 Inhibits Tumor Progression and Mediates Angiogenesis by VEGF Signaling Pathway in Clear Cell Renal Cell Carcinoma.

机构信息

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, Hubei, China.

Institute of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, Hubei, China.

出版信息

Front Biosci (Landmark Ed). 2024 Nov 20;29(11):390. doi: 10.31083/j.fbl2911390.

DOI:10.31083/j.fbl2911390

PMID:39614428

Abstract

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 investigation of the roles played by PLCG2.

RESULTS

Our study has identified a novel biomarker, PLCG2, for ccRCC. 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 and 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.

摘要

背景

透明细胞肾细胞癌（ccRCC）是最常见的肾细胞癌类型。早期 ccRCC 的治疗预后较好，而转移性 ccRCC 患者的五年生存率较低。血管生成是肿瘤转移的基本过程。因此，发现新的血管生成靶点对于提高患者的生存率至关重要。

方法

利用癌症基因组图谱数据库、国际癌症基因组联合会数据库、临床蛋白质组肿瘤分析联合会数据库和血管内皮生长因子（VEGF）信号通路的基因集，鉴定差异表达基因。采用 Western blot（WB）、实时定量聚合酶链反应和免疫组织化学方法验证 ccRCC 组织和细胞中 PLCG2 的下调。通过细胞计数试剂盒-8（CCK-8）测定、Transwell 测定、管形成测定和油红染色来阐明 PLCG2 在肿瘤细胞中的生物学功能。采用基因集富集分析来探索下游通路。通过皮下肿瘤模型和小动物活体荧光成像实验来研究 PLCG2 的作用。

结果

我们的研究确定了一个新的 ccRCC 标志物 PLCG2。通过生物信息学分析验证了 PLCG2 是调节 ccRCC 血管生成的核心基因。研究发现 PLCG2 在 ccRCC 组织和细胞中表达下调。进一步的实验和研究表明 PLCG2 在肿瘤增殖、侵袭、迁移和脂质积累中具有重要作用。管形成测定和 WB 的结果支持 PLCG2 调节 VEGFA 表达和血管生成的作用。