ANGPTL3 Overexpression Suppresses the Development of Oncogenic Properties in Renal Cell Carcinoma via the Wnt/β-Catenin Signaling Pathway and Predicts Good Prognosis.

Yu-Jian Zhang,Fei Feng,Lin Zhang,Qi-Feng Cao,Fu Wang

doi:10.1155/2021/2863856

Abstract

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.

Highlights

Renal cell carcinoma (RCC), accounting for >4% of adult neoplasms, is the most common malignant tumor of the kidney in adults, with a mortality rate [1, 2]
To screen the possible functional regulator involved in RCC progression, we searched “GEPIA” (A online tool analyzing TCGA datasets) [22], finding that the expression of Angiopoietin-like 3 (ANGPTL3) was distinctly decreased in RCC specimens compared with non-tumor renal specimens (Figure 1(a))
We performed RT-PCR using RCC cell lines and found that ANGPTL3 levels were distinctly decreased in RCC cells compared with HK-2 cells (Figure 1(b))

Summary

Introduction

Renal cell carcinoma (RCC), accounting for >4% of adult neoplasms, is the most common malignant tumor of the kidney in adults, with a mortality rate (approximately 45%) [1, 2]. RCC includes several histological subtypes possessing obvious biological characteristics and clinical outcomes [4]. Detection displays a significant benefit for the longterm survival of RCC patients, and patients diagnosed with organ-confined diseases show a five-year survival of >85% [5,6,7]. For those patients with positive metastasis, the 5-year survival is only approximately 10% [8]. There is a crucial need to found new biomarkers and targeted therapies for this aggressive malignancy

Methods

Results

Conclusion