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

Xingyue He,1 Xin Luo,2 Junjun Dong,1 Xing Deng,1 Feng Liu,1,2 Guanghui Wei1,2 1Department of Urology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering; Chongqing Key Laboratory of Pediatrics, Chongqing, People’s Republic of ChinaCorrespondence: Feng Liu; Guanghui WeiDepartment of Urology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of ChinaTel +8613983693965; +8613883617398Email liuu_ff@163.com; u806806@cqmu.edu.cnPurpose: 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