Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer

Abstract 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 reg...

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Main Authors: Yan Li, Qi Wang, Ning Ning, Fanglan Tang, Yan Wang
Format: Article
Language:English
Published: BMC 2020-07-01
Series:Journal of Ovarian Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13048-020-00683-y
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author Yan Li
Qi Wang
Ning Ning
Fanglan Tang
Yan Wang
author_facet Yan Li
Qi Wang
Ning Ning
Fanglan Tang
Yan Wang
author_sort Yan Li
collection DOAJ
description Abstract 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 of MIR502 in 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 of MIR502 were predicted by JASPAR and verified by ChIP-seq data. The LinkedOmics database was used to study genes that were correlated with MIR502. 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 of MIR502 was significantly downregulated in OC, which was related to poor overall survival. NRF1, as an upstream regulator of MIR502, 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 by MIR502, 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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spelling doaj.art-f73f5af00fcd42048989317c776fc7192023-01-03T06:01:12ZengBMCJournal of Ovarian Research1757-22152020-07-0113111610.1186/s13048-020-00683-yBioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancerYan Li0Qi Wang1Ning Ning2Fanglan Tang3Yan Wang4Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical UniversityAbstract 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 of MIR502 in 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 of MIR502 were predicted by JASPAR and verified by ChIP-seq data. The LinkedOmics database was used to study genes that were correlated with MIR502. 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 of MIR502 was significantly downregulated in OC, which was related to poor overall survival. NRF1, as an upstream regulator of MIR502, 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 by MIR502, 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.http://link.springer.com/article/10.1186/s13048-020-00683-yMIR502NRF1Hippo signalling pathwayOvarian cancer
spellingShingle Yan Li
Qi Wang
Ning Ning
Fanglan Tang
Yan Wang
Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer
Journal of Ovarian Research
MIR502
NRF1
Hippo signalling pathway
Ovarian cancer
title Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer
title_full Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer
title_fullStr Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer
title_full_unstemmed Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer
title_short Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer
title_sort bioinformatic analysis reveals mir502 as a potential tumour suppressor in ovarian cancer
topic MIR502
NRF1
Hippo signalling pathway
Ovarian cancer
url http://link.springer.com/article/10.1186/s13048-020-00683-y
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AT fanglantang bioinformaticanalysisrevealsmir502asapotentialtumoursuppressorinovariancancer
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