Frontiers in Genetics (Apr 2022)
The Regulatory Network and Role of the circRNA-miRNA-mRNA ceRNA Network in the Progression and the Immune Response of Wilms Tumor Based on RNA-Seq
- Xiao-Mao Tian,
- Xiao-Mao Tian,
- Xiao-Mao Tian,
- Bin Xiang,
- Bin Xiang,
- Bin Xiang,
- Zhao-Xia Zhang,
- Zhao-Xia Zhang,
- Zhao-Xia Zhang,
- Yan-Ping Li,
- Yan-Ping Li,
- Yan-Ping Li,
- Qin-Lin Shi,
- Qin-Lin Shi,
- Qin-Lin Shi,
- Mu-jie Li,
- Mu-jie Li,
- Mu-jie Li,
- Qi Li,
- Qi Li,
- Qi Li,
- Yi-Hang Yu,
- Yi-Hang Yu,
- Yi-Hang Yu,
- Peng Lu,
- Peng Lu,
- Feng Liu,
- Feng Liu,
- Feng Liu,
- Xing Liu,
- Xing Liu,
- Xing Liu,
- Tao Lin,
- Tao Lin,
- Da-Wei He,
- Da-Wei He,
- Da-Wei He,
- Guang-Hui Wei,
- Guang-Hui Wei,
- Guang-Hui Wei
Affiliations
- Xiao-Mao Tian
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Xiao-Mao Tian
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Xiao-Mao Tian
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Bin Xiang
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Bin Xiang
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Bin Xiang
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Zhao-Xia Zhang
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Zhao-Xia Zhang
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Zhao-Xia Zhang
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Yan-Ping Li
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Yan-Ping Li
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Yan-Ping Li
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Qin-Lin Shi
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Qin-Lin Shi
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Qin-Lin Shi
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Mu-jie Li
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Mu-jie Li
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Mu-jie Li
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Qi Li
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Qi Li
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Qi Li
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Yi-Hang Yu
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Yi-Hang Yu
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Yi-Hang Yu
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Peng Lu
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Peng Lu
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Feng Liu
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Feng Liu
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Feng Liu
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Xing Liu
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Xing Liu
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Xing Liu
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Tao Lin
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Tao Lin
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Da-Wei He
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Da-Wei He
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Da-Wei He
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- Guang-Hui Wei
- Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Guang-Hui Wei
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Guang-Hui Wei
- Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China
- DOI
- https://doi.org/10.3389/fgene.2022.849941
- Journal volume & issue
-
Vol. 13
Abstract
Circular RNA (circRNA), which is a newly discovered non-coding RNA, has been documented to play important roles in miRNA sponges, and the dysregulation of which is involved in cancer development. However, circRNA expression profiles and their role in initiation and progression of Wilms tumor (WT) remain largely unclear at present. Here, we used paired WT samples and high-throughput RNA sequencing to identify differentially expressed circRNAs (DE-circRs) and mRNAs (DE-mRs). A total of 314 DE-circRs and 1612 DE-mRs were identified. The expression of a subset of differentially expressed genes was validated by qRT–PCR. A complete circRNA-miRNA-mRNA network was then constructed based on the common miRNA targets of DE-circRs and DE-mRs identified by miRanda prediction tool. The Gene set enrichment analysis (GSEA) indicated that several signaling pathways involving targeted DE-mRs within the ceRNA network were associated with cell cycle and immune response, which implies their participation in WT development to some extent. Subsequently, these targeted DE-mRs were subjected to implement PPI analysis and to identify 10 hub genes. Four hub genes were closely related to the survival of WT patients. We then filtered prognosis-related hub genes by Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a prognosis-related risk score system based on a three-gene signature, which showed good discrimination and predictive ability for WT patient survival. Additionally, we analyzed the mutational landscape of these genes and the associations between their expression levels and those of immune checkpoint molecules and further demonstrated their potential impact on the efficacy of immunotherapy. qRT–PCR and western blotting (WB) analysis were used to validate key differentially expressed molecules at the RNA and protein levels, respectively. Besides these, we selected a key circRNA, circEYA1, for function validation. Overall, the current study presents the full-scale expression profiles of circRNAs and the circRNA-related ceRNA network in WT for the first time, deepening our understanding of the roles and downstream regulatory mechanisms of circRNAs in WT development and progression. We further constructed a useful immune-related prognostic signature, which could improve clinical outcome prediction and guide individualized treatment.
Keywords
