BACKGROUND Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. RESULTS AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

中文翻译：

---

酰基甘油激酶通过激活肾细胞癌中的 PI3K/AKT/GSK3β 信号通路促进肿瘤生长和转移。

背景技术临床上，转移性肾细胞癌(RCC)患者的中位生存期仅为6-12个月，5年生存率不足20%。因此，深入研究RCC参与的分子机制对于提高晚期RCC患者的生存具有重要意义。酰基甘油激酶（AGK）是一种新发现的脂质激酶，据报道它是一种强效致癌基因，可能参与多种肿瘤恶性进展的调节。然而AGK基因在RCC中的表达和生物学特性仍不清楚。方法 通过实时定量 PCR、Western blotting 和免疫组织化学对 RCC 细胞系和配对患者组织中的 AGK 表达进行定量。采用Kaplan-Meier法和Cox比例风险模型评估AGK在人RCC组织样本中的预后价值。采用卡方检验分析AGK表达与临床病理特征的相关性。利用慢病毒构建了RCC细胞中AGK的稳定过表达和敲低。使用集落形成、贴壁独立生长、EdU 测定、细胞周期分析、伤口愈合、跨孔分析和异种移植肿瘤模型等方法研究 AGK 在人类 RCC 进展中的致癌作用。通过GSEA和KEGG分析检测AGK参与RCC的潜在通路。使用荧光素酶报告基因测定、免疫荧光和体内实验进一步证实了这些结果。结果 AGK在肾细胞癌中表达显着升高，与肾细胞癌的恶性发展和不良预后密切相关。体外和体内实验表明，AGK通过促进细胞周期从G1期向S期的转变来增强RCC细胞的增殖，并通过促进上皮间质转化来增强RCC细胞的迁移和侵袭。AGK 通过激活 RCC 中的 PI3K/AKT/GSK3β 信号通路，可以增加 β-catenin 的核积累，从而进一步上调 TCF/LEF 转录因子活性。结论 AGK通过激活PI3K/AKT/GSK3β信号通路促进RCC进展，可能成为RCC进一步研究的潜在靶点。