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

作者全名："Tian, Xiao-Mao; Xiang, Bin; Zhang, Zhao-Xia; Li, Yan-Ping; Shi, Qin-Lin; Li, Mu-Jie; Li, Qi; Yu, Yi-Hang; Lu, Peng; Liu, Feng; Liu, Xing; Lin, Tao; He, Da-Wei; Wei, Guang-Hui"

作者地址："[Tian, Xiao-Mao; Xiang, Bin; Zhang, Zhao-Xia; Li, Yan-Ping; Shi, Qin-Lin; Li, Mu-Jie; Li, Qi; Yu, Yi-Hang; Lu, Peng; Liu, Feng; Liu, Xing; Lin, Tao; He, Da-Wei; Wei, Guang-Hui] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing, Peoples R China; [Tian, Xiao-Mao; Xiang, Bin; Zhang, Zhao-Xia; Li, Yan-Ping; Shi, Qin-Lin; Li, Mu-Jie; Li, Qi; Yu, Yi-Hang; Lu, Peng; Liu, Feng; Liu, Xing; Lin, Tao; He, Da-Wei; Wei, Guang-Hui] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Childrens Hosp,China Int Sci & Techno, Chongqing Key Lab Pediat,Key Lab Child Dev & Diso, Chongqing, Peoples R China; [Tian, Xiao-Mao; Xiang, Bin; Zhang, Zhao-Xia; Li, Yan-Ping; Shi, Qin-Lin; Li, Mu-Jie; Li, Qi; Yu, Yi-Hang; Liu, Feng; Liu, Xing; He, Da-Wei; Wei, Guang-Hui] Chongqing Key Lab Children Urogenital Dev & Tissu, Chongqing, Peoples R China"

通信作者："Liu, F (通讯作者)，Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing, Peoples R China.; Liu, F (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Childrens Hosp,China Int Sci & Techno, Chongqing Key Lab Pediat,Key Lab Child Dev & Diso, Chongqing, Peoples R China.; Liu, F (通讯作者)，Chongqing Key Lab Children Urogenital Dev & Tissu, Chongqing, Peoples R China."

来源：FRONTIERS IN GENETICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000850087800001

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：wilms tumor; circular RNA; ceRNA; RNA sequencing; prognosis; biomarker; immune microenvironment

摘要："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 VVT 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 VVT 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 VVT development and progression. We further constructed a useful immune-related prognostic signature, which could improve clinical outcome prediction and guide individualized treatment."

基金机构：Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0345]; Medical Scientific Research Project of Chongqing [2022GDRC009]; general project of clinical medicine research of Children's Hospital of Chongqing Medical University [NCRC-2019-GP-08]

基金资助正文："This work was supported by the Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0345), the Medical Scientific Research Project of Chongqing (NO.2022GDRC009), and the general project of clinical medicine research of Children's Hospital of Chongqing Medical University (NCRC-2019-GP-08)."