期刊
JOURNAL OF OVARIAN RESEARCH
卷 13, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13048-020-00683-y
关键词
MIR502; NRF1; Hippo signalling pathway; Ovarian cancer
Background Ovarian cancer (OC) is a major cause of death among women due to the lack of early screening methods and its complex pathological progression. Increasing evidence has indicated that microRNAs regulate gene expression in tumours by interacting with mRNAs. Although the research regarding OC and microRNAs is extensive, the vital role ofMIR502in OC remains unclear. Methods We integrated two microRNA expression arrays from GEO to identify differentially expressed genes. The Kaplan-Meier method was used to screen for miRNAs that had an influence on survival outcome. Upstream regulators ofMIR502were predicted by JASPAR and verified by ChIP-seq data. The LinkedOmics database was used to study genes that were correlated withMIR502. Gene Set Enrichment Analysis (GSEA) was conducted for functional annotation with GO and KEGG pathway enrichment analyses by using the open access WebGestalt tool. We constructed a PPI network by using STRING to further explore the core proteins. Results We found that the expression level ofMIR502was significantly downregulated in OC, which was related to poor overall survival. NRF1, as an upstream regulator ofMIR502, was predicted by JASPAR and verified by ChIP-seq data. In addition, anti-apoptosis and pro-proliferation genes in the Hippo signalling pathway, including CCND1, MYC, FGF1 and GLI2, were negatively regulated byMIR502, as shown in the GO and KEGG pathway enrichment results. The PPI network further demonstrated that CCND1 and MYCN were at core positions in the development of ovarian cancer. Conclusions MIR502, which is regulated by NRF1, acts as a tumour suppressor gene to accelerate apoptosis and suppress proliferation by targeting the Hippo signalling pathway in ovarian cancer.
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