ArticleNan fang yi ke da xue xue bao = Journal of Southern Medical University2023
[Identification of key molecules in miRNA-mRNA regulatory network associated with high-grade serous ovarian cancer recurrence using bioinformatic analysis].
Article in Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo investigate the correlation of the potential functional microRNA (miRNA)-mRNA regulatory network with recurrence of high-grade serous ovarian carcinoma (HGSOC) and its biological significance.
methodsThis study was performed based on the data of 354 patients with HGSOC from the Cancer Genome Atlas database. In these patients, HGSOC was divided into different subtypes based on the pathways identified by GO analysis, and the correlations of the subtypes with HGSOC recurrence and differentially expressed miRNAs and mRNAs were assessed. Two relapse-related datasets were identified using the Gene Set Enrichment (GSE) database, from which the differentially expressed miRNAs were identified by intersection with the TCGA data. The target genes of these miRNAs were predicted using miRWalk 2.0 database, and these common differentially expressed miRNAs and mRNAs were used to construct the key miRNA-mRNA network associated with HGSOC recurrence. The expression of miR-506-3p and SNAI2 in two ovarian cancer cell lines was detected using RT-qPCR and Western blotting, and their targeted binding was verified using a double luciferase assay. The effect of miR-506-3p expression modulation on ovarian cancer cell migration was detected using scratch assay and Transwell assay.
resultsWe screened 303 GO terms of HGSOC-related pathways and identified two HGSOC subtypes (C1 and C2). The subtype C1 was associated with a significantly higher recurrence rate than C2. The differentially expressed genes between C1 and C2 subtypes were mainly enriched in epithelial-mesenchymal transition (EMT). Five miRNAs were identified as potential regulators of EMT, and a total of 41 target genes were found to be involved in the differential expressions of EMT pathway between C1 and C2 subtypes. The key miRNA-mRNA network associated with HGSOC recurrence was constructed based on these 5 miRNAs and 41 mRNAs. MiR-506-3p was confirmed to bind to SNAI2, and up-regulation of miR-506-3p significantly inhibited SNAI2 expression and reduced migration and invasion of SKOV3 and CAOV3 cells (
conclusionMiR-506-3p and SNAI2 are the key molecules associated with HGSOC recurrence. MiR-506-3p may affect EMT of ovarian cancer cells by regulating cell migration and invasion via SNAI2, and its expression level has predictive value for HGSOC recurrence.
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