Zhi-Min Deng1, Fang-Fang Dai1, Quan Zhou2, Yan-Xiang Cheng3. 1. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P.R. China. 2. Department of Obstetrics and Gynecology, the People's Hospital of China Three Gorges University/the First People's Hospital of Yichang, Yichang, Hubei, 443000, P.R. China. zhouquan8519@163.com. 3. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P.R. China. rm001050@whu.edu.cn.
Abstract
BACKGROUND: With the broadened application of gene expression profiles analysis, the role of miRNA and circRNA are of increasing concern in recent years, especially during the pathogenesis of cancer. However, to date, the reported on this area in cervical cancer are limited. METHOD: In this study, Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis were utilized to screen out differentially expressed (DE) circular RNAs in cervical cancer, and then we predicted and screened the combined microRNAs (miRNA) and downstream mRNAs to construct circular (circ)RNA-miRNA-mRNA network. RESULT: As a result, a regulatory circular (circ)RNA-miRNA-mRNA with 1 circRNA node, 4 miRNA nodes, 135 mRNA nodes were constructed in an attempt to provide novel biomarkers for the pathogenesis of cervical cancer. In addition, enrichment analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on mRNAs in the network. After further screening of mRNAs by two online databases of GEPIA2 and RNAyhrid, precise target genes were obtained. Next, we screened out four target genes (CXCL16, IRF4, OAS3 and PTGER3) by constructing the protein-protein interaction (PPI) network, and mapped them to the initial network to reconstruct the circRNA-miRNA-mRNA network. Notably, the low expression of IRF4 was demonstrated to be associated with a significantly poorer overall survival in the GEPIA2 database, which was also verified by the immunofluorescence of the sections in Human Protein Atlas (HPA). The upstream miRNA corresponding to IRF4 is hsa-miR-1228-3p. CONCLUSION: From above concern, it can conclude that hsa_circ_0000301/hsa-miR-1228-3p/IRF4 may be involved in the occurrence and development of cervical cancer. However, the specific mechanism should be further studied and confirmed.
BACKGROUND: With the broadened application of gene expression profiles analysis, the role of miRNA and circRNA are of increasing concern in recent years, especially during the pathogenesis of cancer. However, to date, the reported on this area in cervical cancer are limited. METHOD: In this study, Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis were utilized to screen out differentially expressed (DE) circular RNAs in cervical cancer, and then we predicted and screened the combined microRNAs (miRNA) and downstream mRNAs to construct circular (circ)RNA-miRNA-mRNA network. RESULT: As a result, a regulatory circular (circ)RNA-miRNA-mRNA with 1 circRNA node, 4 miRNA nodes, 135 mRNA nodes were constructed in an attempt to provide novel biomarkers for the pathogenesis of cervical cancer. In addition, enrichment analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on mRNAs in the network. After further screening of mRNAs by two online databases of GEPIA2 and RNAyhrid, precise target genes were obtained. Next, we screened out four target genes (CXCL16, IRF4, OAS3 and PTGER3) by constructing the protein-protein interaction (PPI) network, and mapped them to the initial network to reconstruct the circRNA-miRNA-mRNA network. Notably, the low expression of IRF4 was demonstrated to be associated with a significantly poorer overall survival in the GEPIA2 database, which was also verified by the immunofluorescence of the sections in Human Protein Atlas (HPA). The upstream miRNA corresponding to IRF4 is hsa-miR-1228-3p. CONCLUSION: From above concern, it can conclude that hsa_circ_0000301/hsa-miR-1228-3p/IRF4 may be involved in the occurrence and development of cervical cancer. However, the specific mechanism should be further studied and confirmed.
Authors: Matthew E Ritchie; Belinda Phipson; Di Wu; Yifang Hu; Charity W Law; Wei Shi; Gordon K Smyth Journal: Nucleic Acids Res Date: 2015-01-20 Impact factor: 16.971