MIR502 Acts As a Tumor Suppressor Gene to Accelerate Apoptosis and Suppress Proliferation by Targeting Hippo Signaling Pathway in Ovarian Cancer
Abstract Background Ovarian cancer (OC) is the major cause of death among women due to the lack of early screening methods and complex pathological progression. Increasing evidence indicated that microRNAs were considered as gene expression regulators in tumors by interacting with mRNAs. Although researches regarding with OC and microRNAs are extensive, the vital role of MIR502 in OC still remains unclear.Methods We integrated two microRNA expression arrays from GEO to identify differentially expressed genes. Kaplan–Meier method was used to screen miRNAs that had influence on survival outcome. Upstream regulator of MIR502 was predicted by JASPAR and verified by ChIP-seq data. The LinkedOmics database was used to study correlated genes with MIR502. Gene Set Enrichment Analysis (GSEA) was conducted to reveal the functional annotation of GO and KEGG pathway enrichment analysis by using the open access WebGestalt tool. We constructed PPI network by using the STRING to further explore core protein.Results We found that expression level of MIR502 was significantly down regulated in OC, which was related to poor overall survival outcome. NRF1 as the upstream regulator of MIR502 was predicted by JASPAR and verified by ChIP-seq data. In addition, anti-apoptosis and pro-proliferation genes attending in Hippo signaling pathway, including CCND1, MYC, FGF1 and GLI2 were negatively regulated by MIR502 in the analysis of GO and KEGG pathway enrichment results. PPI network further demonstrated that CCND1 and MYCN were at core position in the development of ovarian cancer.Conclusions MIR502, which was regulated by NRF1, acted as a tumor suppressor gene to accelerate apoptosis and suppress proliferation by targeting Hippo signaling pathway in ovarian cancer.