Dataset Information

Identification of common differentially-expressed miRNAs in ovarian cancer cells and their exosomes compared with normal ovarian surface epithelial cell cells.

ABSTRACT: The aim of the present study was to identify common microRNAs (miRNAs) in ovarian cancer (OC) cells and their exosomes using microarray data (accession number GSE76449) available from the Gene Expression Omnibus database, including exosomal samples from 3 OC cell lines, 1 normal ovarian surface epithelial cell line and their original cell samples. Differentially-expressed miRNAs (DE-miRNAs) were identified using the Linear Models for Microarray data method, and mRNA targets of DE-miRNAs were predicted using the miRWalk2 database. The potential functions of the target genes of the DE-miRNAs were analyzed using the Database for Annotation, Visualization and Integrated Discovery tool. The association between crucial miRNAs and target genes, and their clinical associations, were validated using The Cancer Genome Atlas data. As a result, 12 upregulated and 12 downregulated DE-miRNAs were shared by the 3 OC cell lines compared with normal controls in the exosomal samples, while 5 upregulated and 65 downregulated DE-miRNAs were shared between the original cells. Among them, 9 downregulated DE-miRNAs were shared between exosomal and original cells. The target genes of 4 common DE-miRNAs between exosomal and original cells (miR-127-3p, miR-339-5p, miR-409-3p and miR-654-3p) were predicted. Functional enrichment analysis indicated that these target genes may be involved in the Wnt signaling pathway (miR-409-3p-CTBP1 and miR-339-5p-CHD8) and Proteoglycans in cancer (miR-127-3p-PPP1CA). The negative associations between these 3 miRNAs and target genes were confirmed by a Pearson's correlation analysis. miR-127 was negatively associated with tumor grade. In conclusion, our results describe a set of miRNAs involved in OC development, in exosomal and non-exosomal manners, by regulating their target genes. They may be potential targets for treatment of OC.

SUBMITTER: Zhang S

PROVIDER: S-EPMC6036573 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Identification of common differentially-expressed miRNAs in ovarian cancer cells and their exosomes compared with normal ovarian surface epithelial cell cells.

Zhang Shitao S Zhang Xiaoping X Fu Xueqi X Li Wannan W Xing Shu S Yang Yiling Y

Oncology letters 20180612 2

The aim of the present study was to identify common microRNAs (miRNAs) in ovarian cancer (OC) cells and their exosomes using microarray data (accession number GSE76449) available from the Gene Expression Omnibus database, including exosomal samples from 3 OC cell lines, 1 normal ovarian surface epithelial cell line and their original cell samples. Differentially-expressed miRNAs (DE-miRNAs) were identified using the Linear Models for Microarray data method, and mRNA targets of DE-miRNAs were pre ...[more]

PMID: 30013629

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Project description:PurposeOvarian cancer, manifested by malignant ascites, is the most lethal gynaecological cancer. Suspended ascites-derived spheroids may contribute to ovarian cancer metastasis. MicroRNAs (miRNAs) are also associated with ovarian cancer metastasis. Here, we aimed to investigate the differentially expressed miRNAs (DE-miRNAs) in ascites-derived spheroids compared with primary tumour tissues, which may regulate ovarian cancer metastasis.MethodsThe DE-miRNAs between ovarian cancer primary tumour tissues and ascites-derived spheroids were identified by GEO2R screening in samples from 3 high-grade serous ovarian cancer (HGSOC) patients of dataset GSE65819. We used MiRTarBase, TargetScanHuman7.2 and STRING to predict the target hub genes of DE-miRNAs and DAVID to perform functional analysis of hub genes. ALGGEN PROMO and TransmiR v2.0 were used to predict transcription factors (TFs) that potentially regulate DE-miRNAs expression. The observed differences in DE-miRNAs expression were validated with samples from 12 HGSOC patients and 2 ovarian cancer cell lines using PCR. The functions of DE-miRNAs on ovarian cancer progression were verified by invasion, adherent, and angiogenesis assays.ResultsThrough bioinformatics screening and experimental validation, miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p were identified as being significantly downregulated in ascites-derived spheroids compared with primary tumour tissues. In addition, TFAP2A was identified as a potentially common upstream TF regulating the expression of the above mentioned DE-miRNAs. The overexpression of miR-199a-3p, miR-199b-3p, miR-199a-5p lead to invasion inhibition, and the overexpression of miR-126-3p, miR-145-5p, miR-199a-5p and miR-199b-3p lead to adhesion inhibition of suspended ovarian cancer cells. High-expressed miR-126-3p, miR-199a-3p, miR-199a-5p and miR-199b-3p contributed to apoptosis of suspended ovarian cancer cells.ConclusionThe downregulated expression of miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p in ascites-derived spheroids plays a key role in promoting ovarian cancer progression, which may represent novel molecules for targeted therapy for ovarian cancer.

Dataset Information

Identification of common differentially-expressed miRNAs in ovarian cancer cells and their exosomes compared with normal ovarian surface epithelial cell cells.

Publications

Identification of common differentially-expressed miRNAs in ovarian cancer cells and their exosomes compared with normal ovarian surface epithelial cell cells.

Similar Datasets

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