CENPA promotes clear cell renal cell carcinoma progression and metastasis via Wnt/\u03b2-catenin signaling pathway

Qi Wang,Tianbo Xu,Jian Shi,Jiaping Chen,Changjie Yue,Yi Shou,Xiong Yang,Zhiyong Xiong,Huageng Liang,Hongmei Yang,Xiaoping Zhang,Di Liu,Jiaju Xu,Jingchong Liu,Yuenan Liu

doi:10.1186/s12967-021-03087-8

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney. New and reliable biomarkers are in urgent need for ccRCC diagnosis and prognosis. The CENP family is overexpressed in many types of cancers, but its functions in ccRCC have not been fully clarified. In this paper, we found that several CENP family members were highly expressed in ccRCC tissues. Also, CENPA expression level was related to clinicopathological grade and prognosis by weighted gene co-expression network analysis (WGCNA). CENPA served as a representative CENP family member as a ccRCC biomarker. Further in vitro experiments verified that overexpression of CENPA promoted ccRCC proliferation and metastasis by accelerating the cell cycle and activating the Wnt/β-catenin signaling pathway. The elevated β-catenin led by CENPA overexpression translocated to nucleus for downstream effect. Functional recovery experiment confirmed that Wnt/β-catenin pathway was essential for ccRCC progression and metastasis. Developing selective drugs targeting CENPA may be a promising direction for cancer treatment.

Highlights

Renal carcinoma is a malignancy in urinary system with high incidence
CENPA was identified as a hub gene in Clear cell renal cell cancer (ccRCC) via weighted gene co-expression network analysis (WGCNA) To find the hub genes for ccRCC from the analyzed gene set, 6137 genes were identified as differentially expressed genes (DEGs) by the “limma” package according to the cutoff criterion
Eight members (CENPA, CENPE, CENPF, CENPH, CENPI, CENPK, CENPM, CENPU) of the Centromere protein (CENP) family were all upregulated in Kidney renal clear cell carcinoma (KIRC) cohort from TCGA (The Cancer Genome Atlas) database (Fig. 2A)

Summary

Introduction

Renal carcinoma is a malignancy in urinary system with high incidence. As reported by the American Cancer Society’s most recent estimates about renal malignancies in the United States for 2020, approximately 76,080 new cases of kidney and renal pelvis cancer would be diagnosed, and approximately 13,780 people would die from this disease [1]. Renal cell carcinoma (RCC) accounts for 90% of all renal malignancies [2]. Clear cell renal cell cancer (ccRCC) is a major and malignant subtype of renal carcinoma, accounting for approximately 3/4 of RCC [3]. CcRCC’s diagnostic technique has been greatly improved, approximately one in three patients have advanced tumor when first diagnosed still have distant metastasis at the time of diagnosis [4]. These patients may have a worse prognosis due to missing the timing for surgery. Radiotherapy and traditional chemotherapy are not as effective for ccRCC, which is why targeted therapy has been developed. It is imperative to look for new biomarkers for early diagnosis and targeted therapy

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