CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma

Du-Chu Chen,Liang Peng,Bin Yu,Yuxin Gao,Ya-Wei Yan,Xin-Xing Zhu,Jingying Huang,Yi-Ze Wang,Min Liu,Demeng Chen,Yasmeen Saeed,You-De Liang,Jiaqi Liu,Yi-Zhou Jiang,Chun-Zhi Ai

doi:10.1186/s12935-017-0473-z

Abstract

BackgroundRenal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment.MethodsOncoLnc was used as a tool for interactively exploring survival correlations. Gene manipulation and expression analysis were carried out using siRNA, RT-PCR and Western blotting. Wound healing and invasion assays were used for phenotypical characterization. Aldefluor assay and FACS sorting Sphere culture were used to determine the “stemness” of CSCs. Co-Immunoprecipitation (Co-IP) was used to examine the interaction between OCT4 and CBFA2T2. Student’s t-test and Chi square test was used to analyze statistical significance.ResultsCBFA2T2 expression can significantly predict the survival of RCC patients. Knocking-down of CBFA2T2 can inhibit cell migration and invasion in RCC cells in vitro, and reduce ALDHhigh CSCs populations. CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines.ConclusionsOur data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

Highlights

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90% of all primary kidney cancer
Association between CBFA2T2 and stem cell factors expression with the prognosis of RCC patients To examine the association of the expression levels of CBFA2T2, as well as several important cancer stem cells factors, including SOX2, OCT4, CD133, NANOG and ALDH1A3, with the and prognosis of patients with RCC, Kaplan–Meier survival analyses were performed on patients in the high and low expression groups between these gene expression and clinical outcomes on the homepage of oncolnc [23]
Higher levels of OCT-4, ALDH1A3, NANOG and SALL4 expression were associated with worse survival (p = 0.048, p = 0.00228, p = 2.46e−05 and p = 3.98e−07, respectively) of RCC patients (Fig. 1b–e)

Summary

Introduction

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Renal cell carcinoma (RCC) represents one of the most common type of kidney cancer, accounting for 90% of adult renal malignancies [1]. The prognosis of advanced RCC is very poor, with a 5-year survival rate of 5–10% [3]. Recent studies have shown the presence of cancer stem cells (CSCs) in various solid tumor tissues [5,6,7]. CSCs promote cancer resistance to treatment and recurrence, leading to high mortality [6]. CSC-targeted therapy can be an essential part of cancer therapy

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Conclusion