Department of Urology, Dafeng People's Hospital, Dafeng, 224100 Yancheng, Jiangsu, China.
Department of Urology, The Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200092, Yangpu, Shanghai, China.
Dis Markers. 2021 Aug 24;2021:2863856. doi: 10.1155/2021/2863856. eCollection 2021.
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/-catenin signaling using TOP/FOP flash reporter assays and western blot. The results showed that overexpression of ANGPTL3 distinctly suppressed the activity of Wnt/-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/-catenin pathway. ANGPTL3 may be a novel therapeutic target and a prognostic biomarker for RCC patients.
血管生成素样蛋白 3(ANGPTL3)参与新血管生长,据报道在许多不同的癌症中表现出异常表达。然而,ANGPTL3 在肾细胞癌(RCC)中的表达模式和功能很少有报道。在这项研究中,我们观察到 TCGA 数据集和细胞系中的 RCC 标本中 ANGPTL3 的表达明显下调。生存分析还表明,ANGPTL3 低表达的患者总生存和无病生存时间短于 ANGPTL3 高表达的患者。细胞计数试剂盒-8(CCK-8)检测、集落形成实验和流式细胞术显示,过表达 ANGPTL3 明显抑制 RCC 细胞的增殖,并促进细胞凋亡。Transwell 检测和划痕愈合检测显示,ANGPTL3 上调抑制 RCC 细胞的迁移和侵袭。然后,我们使用 TOP/FOP flash 报告基因检测和 Western blot 探索了 ANGPTL3 失调是否影响 Wnt/-catenin 信号通路的改变。结果表明,过表达 ANGPTL3 明显抑制了 Wnt/-catenin 信号通路的活性。总的来说,我们的研究结果证实,过表达 ANGPTL3 与 RCC 患者的恶性程度和良好预后有关,ANGPTL3 上调通过 Wnt/-catenin 通路抑制肿瘤的增殖和转移。ANGPTL3 可能成为 RCC 患者的一种新的治疗靶点和预后生物标志物。