Inhibition of KIF20A by transcription factor IRF6 affects the progression of renal clear cell carcinoma

Xinwei Ma,Hongquan Pang,Jianming Xu,Xiaoqi Wang,Junkang Shen,Jianbing Zhu,Qian Dong

doi:10.1186/s12935-021-01879-y

Abstract

BackgroundRenal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, although there is yet no report on its expression in ccRCC.MethodsThe expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP databases. In addition, GEPIA database predicted the relationship between IRF6 and KIF20A expressions and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP assays. The specific effects of IRF6 on ccRCC cell proliferation, invasion and apoptosis were subsequently examined at both cellular level and animal level.ResultsThe database predicted down-regulated IRF6 expression in renal carcinoma tissues and its correlation with poor prognosis. IRF6 overexpression inhibited cRCC cell proliferation, invasion and migration. In addition, up-regulated KIF20A expression in renal carcinoma tissues and its association with prognosis were also predicted. Interference with KIF20A inhibited the proliferation, invasion, and migration of ccRCC cells. Finally, we confirmed that KIF20A is a functional target of IRF6 and can partially reverse the effects of IRF6 on the proliferation, invasion and migration of ccRCC cells. Conclusion: Inhibition of KIF20A by transcription factor IRF6 affects cell proliferation, invasion and migration in renal clear cell carcinoma.

Highlights

Renal cell carcinoma, known as kidney cancer, ranks among the top ten cancers in the world and accounts for 2% of total cancer incidence worldwide with the numberInterferon Regulatory Factor 6 (IRF6) is a member of the interferon regulatory factor family
Expression of IRF6 in renal carcinoma tissues and its relationship with prognosis Through Gene Expression Profiling Interactive Analysis (GEPIA) database, we predicted the expression of IRF6 in the tissues of patients with kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), and kidney renal papillary cell carcinoma (KIRP)
Our investigation on the basis of GEPIA data demonstrated that IRF6 expression was correlated strongly with the pathological stage of renal clear cell carcinoma (Fig. 1c)

Summary

Introduction

Known as kidney cancer, ranks among the top ten cancers in the world and accounts for 2% of total cancer incidence worldwide with the numberInterferon Regulatory Factor 6 (IRF6) is a member of the interferon regulatory factor family. The expression product of IRF6 is transcription factor, which can regulate cell proliferation, cycle and differentiation [4,5,6]. IRF6 plays an important role in tumor genesis. Decreased expression of IRF6 is found in highly metastatic nasopharyngeal carcinoma cells, while its overexpression proves to inhibit tumor cell proliferation and growth and enhances their chemotherapeutic sensitivity [8]. The expression of IRF6 in ccRCC has not been reported. Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, there is yet no report on its expression in ccRCC

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Conclusion