CORO6 Promotes Cell Growth and Invasion of Clear Cell Renal Cell Carcinoma via Activation of WNT Signaling

Abstract

BackgroundRenal cell carcinoma (RCC) constitutes the most lethal type of genitourinary cancer. Understanding of RCC tumor biology helps to identify novel targets and develop directed treatments for patients with this type of cancer. MethodsBioinformatical Analysis of The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset. Western blotting and qPCR were used to examine the expression levels of interested genes. Flow cytometry, MTT, BrdU staining, wound healing assay and transwell invasion assay were applied to determine the biological functions of CORO6 in ccRCC cells. The in vivo effect of CORO6 on ccRCC development was validated with xenografted mouse model.ResultsAnalysis from both The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset and our RCC samples demonstrated that the expression level of CORO6 was significantly higher in RCC patients than in normal kidney tissues, and its level was highly associated with tumor stage and grade. Importantly, CORO6 expression level was an independent predictor of tumor metastasis and overall survival in RCC patients. Our cell line data also confirmed that CORO6 knockdown could suppress RCC cell growth as well as cell migration and invasion. The depletion of CORO6 led to cell cycle arrest at the G0/G1 phase and caused cell apoptosis. Further, mechanistic dissection showed that CORO6 mediated RCC cell growth, and cell invasion relied on WNT signaling. Moreover, the in vivo data suggested that CORO6 knockdown indeed suppressed RCC tumor growth. ConclusionsOverall, our study defines the oncogenic role of CORO6 in RCC progression and provides a rationale for developing CORO6-targeted therapies for improved treatment of RCC patients.

NEK2 Serves as a Novel Biomarker and Enhances the Tumorigenicity of Clear-CellRenal-Cell Carcinoma by Activating WNT/β-Catenin Pathway

“…Additionally, MMP-9 is one of the Wnt pathway target genes, which can be transcriptionally regulated [31]. According to some substantial studies, the WNT/β-catenin pathway is hyperactivated in ccRCC, and targeted inhibition of the WNT/β-catenin pathway may become a feasible therapeutic strategy for tumors [32][33][34]. Here, our results showed that NEK2 silencing could obviously downregulate the protein expression levels of key proteins, such as p-GSK-3β, β-catenin, and the downstream regulator c-Myc, proving that NEK2 silencing could inhibit the WNT/β-catenin signaling pathway.…”