Long Non-Coding RNA XIST Promotes Wilms Tumor Progression Through the miR-194-5p/YAP Axis

Abstract

Purpose

Although the long non-coding RNA (lncRNA) X inactive-specific transcript (XIST) has been reported to have an anti-tumor effect in multiple malignant tumors, its role in Wilms tumor (WT) progression has not been characterized. Thus, we investigated the underlying mechanism by which XIST regulates WT progression.

Patients and Methods

We performed microarray analysis and real-time quantitative PCR (RT-qPCR) to detect the expression levels of XIST lncRNA, microRNA-194-5p (miR-194-5p), and YAP (yes-associated protein in Hippo pathway) in tumor and matched adjacent normal tissues and blood collected from 49 WT patients. We also conducted bioinformatics analyses to identify differentially expressed genes. We measured the effects of XIST overexpression and knockdown on cell proliferation, apoptosis, migration, and invasion, and its association with the miR-194-5p/YAP pathway in the rhabdoid G401cell line using flow cytometry, transwell assays, immunohistochemistry, Western blot analysis, and the dual luciferase reporter gene assay.

Results

We found that XIST lncRNA levels were increased in blood and tissue samples of WT patients, and this upregulation was significantly correlated with TNM staging and shorter survival time. Notably, we found that XIST upregulation correlated with miR-194-5p downregulation and YAP upregulation in WT tissues, suggesting that XIST regulates the miR-194-5p/YAP pathway. Conversely, XIST downregulation inhibited WT cell proliferation, migration, and invasion and induced apoptosis. Our study revealed the oncogenic role of the lncRNA XIST in WT and demonstrated its role as a competitive endogenous RNA that regulates the miR-194-5p/YAP pathway.

Conclusion

Our study demonstrates XIST’s potential as a clinical prognostic biomarker and therapeutic target for WT.

Keywords:

• lncRNA
• XIST
• Wilms tumor
• YAP

Data Sharing Statement

The sequencing data can be accessed on the GEO database (GSE166606). Data generated in the current study are available from the corresponding authors Feng Liu and Guanghui Wei upon reasonable request.

Ethics Approval and Consent to Participate

This study was conducted with approval from the Ethics Committee of the Research Institution of Children’s Hospital of Chongqing Medical University, and this study was conducted in accordance with the Declaration of Helsinki. The written informed consent was obtained from all parents of patients.

Author Contributions

All authors made substantial contributions to the conception and design, data acquisition, analysis and interpretation, and drafting and editing the manuscript; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.