Upregulation of homeobox D10 expression suppresses invasion and migration of clear cell renal cell carcinoma through targeting of E-cadherin

Zongtao Ren,Yunfeng Niu,Aili Zhang,Bo Fan

doi:10.1007/s11033-021-06993-8

Zongtao Ren, Yunfeng Niu + Show 2 more

Open Access

https://doi.org/10.1007/s11033-021-06993-8

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Abstract

BackgroundClear cell renal cell carcinoma (CCRCC) is one of the most common types of renal cell carcinoma. Accumulating evidence indicates that homeobox D10 (HOXD10) acts as a tumor suppressor or oncogene in various carcinomas. However, the regulation and potential mechanisms of HOXD10 in CCRCC remain largely unknown.PurposeTo explore the effect and potential mechanism of HOXD10 on the invasion and migration of CCRCC cells.MethodsThe expression of HOXD10, E-cadherin and other epithelial mesenchymal transition (EMT)-related proteins was assessed by reverse transcription-quantitative real-time PCR (qRT-PCR) and Western blots. A series of functional assays were performed in RCC cell lines to explore the function of HOXD10 in CCRCC progression. Bioinformatics analysis, ChIP assays, and dual luciferase reporter assays were utilized to identify the interaction between HOXD10 and E-cadherin.ResultsLow expression of HOXD10 and E-cadherin was observed in CCRCC tissues and ACHN and 786-O cells. Downregulation of HOXD10 expression was correlated with the TNM stage of CCRCC patients. Functional experiments demonstrated that malignant biological ability was significantly inhibited by HOXD10 overexpression in RCC cells. Moreover, E-cadherin was a potential target gene of HOXD10, as evidenced by a series of assays. In addition, overexpression of HOXD10 inhibited the progression of CCRCC by regulating the expression of E-cadherin, vimentin, and β-catenin in vitro.ConclusionHOXD10 acts as a tumor suppressor and suppresses invasion and migration of CCRCC cells by regulating E-cadherin and EMT processes. Thus, targeting HOXD10 may be a therapeutic strategy for CCRCC treatment.

Highlights

Renal cell carcinoma (RCC) is one of the most common tumors of the kidney and arises from the epithelium of the renal tubules [1]
homeobox D10 (HOXD10) expression was downregulated in Clear cell renal cell carcinoma (CCRCC) tissues and RCC cell lines
To verify whether HOXD10 plays a role in the occurrence and progression of CCRCC, we used the StarBase-V3.0 database to demonstrate that the expression level of HOXD10 was downregulated in CCRCC tissues compared with the corresponding normal renal tissues (Supplementary Fig. S1)

Summary

Introduction

Renal cell carcinoma (RCC) is one of the most common tumors of the kidney and arises from the epithelium of the renal tubules [1]. Accumulating studies indicate that dysfunction of HOX transcription factors plays key roles in the progression of various types of carcinomas [5]. Accumulating evidence indicates that homeobox D10 (HOXD10) acts as a tumor suppressor or oncogene in various carcinomas. Purpose To explore the effect and potential mechanism of HOXD10 on the invasion and migration of CCRCC cells. A series of functional assays were performed in RCC cell lines to explore the function of HOXD10 in CCRCC progression. E-cadherin was a potential target gene of HOXD10, as evidenced by a series of assays. Overexpression of HOXD10 inhibited the progression of CCRCC by regulating the expression of E-cadherin, vimentin, and β-catenin in vitro. Conclusion HOXD10 acts as a tumor suppressor and suppresses invasion and migration of CCRCC cells by regulating E-cadherin and EMT processes. Targeting HOXD10 may be a therapeutic strategy for CCRCC treatment

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