Angiopoietin-like 3 (ANGPTL3), which is involved in new blood vessel growth, has been reported to exhibit an abnroaml expression in many different cancers. However, the expressing pattern and functions of ANGPTL3 renal cell carcinoma (RCC) were rarely reported. In this study, we observed that ANGPTL3 expression was distinctly downregulated in both RCC specimens from TCGA datasets and cell lines. Survival assays also revealed that patients with low ANGPTL3 expression exhibited a shorter overall survival and disease-free survival than those with high ANGPTL3 expression. Cell counting kit-8 (CCK-8) assay, Colony formation assay, and flow cytometry showed that overexpression of ANGPTL3 distinctly suppressed the proliferation of RCC cells, and promoted apoptosis. Transwell assays and Wound healing assays revealed that ANGPTL3 upregulation suppressed the migration and invasion of RCC cells. Then, we explored whether ANGPTL3 dysregulation influenced the alteration of Wnt/β-catenin signaling using TOP/FOP flash reporter assays and western blot. The results showed that overexpression of ANGPTL3 distinctly suppressed the activity of Wnt/β-catenin signaling. Overall, our results confirmed that overexpression of ANGPTL3 was related to the malignancy and good prognosis of RCC patients, and ANGPTL3 upregulation inhibited the tumor proliferation and metastasis via the Wnt/β-catenin pathway. ANGPTL3 may be a novel therapeutic target and a prognostic biomarker for RCC patients.

中文翻译：

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ANGPTL3 过表达通过 Wnt/β-连环蛋白信号通路抑制肾细胞癌致癌特性的发展并预测良好的预后

据报道，参与新血管生长的血管生成素样 3 (ANGPTL3) 在许多不同的癌症中表现出异常表达。然而，ANGPTL3肾细胞癌（RCC）的表达模式和功能却鲜有报道。在这项研究中，我们观察到来自 TCGA 数据集和细胞系的 RCC 标本中 ANGPTL3 表达明显下调。生存分析还显示，ANGPTL3 低表达患者的总生存期和无病生存期短于 ANGPTL3 高表达患者。细胞计数 kit-8 (CCK-8) 测定、集落形成测定和流式细胞术表明，ANGPTL3 的过表达明显抑制 RCC 细胞的增殖，并促进细胞凋亡。Transwell 检测和伤口愈合检测显示 ANGPTL3 上调抑制了 RCC 细胞的迁移和侵袭。然后，我们探讨了 ANGPTL3 失调是否影响 Wnt/使用 TOP/FOP 快速报告基因检测和蛋白质印迹的β -连环蛋白信号传导。结果表明，ANGPTL3的过表达明显抑制了Wnt/ β -catenin信号的活性。总体而言，我们的研究结果证实ANGPTL3的过表达与RCC患者的恶性程度和预后良好有关，而ANGPTL3的上调通过Wnt/ β -catenin通路抑制肿瘤的增殖和转移。ANGPTL3 可能是 RCC 患者的新型治疗靶点和预后生物标志物。