Downregulation of miR-145-5p in cancer cells and their derived exosomes may contribute to the development of ovarian cancer by targeting CT

摘要

The present study aimed to identify shared microRNAs (miRNAs) in ovarian cancer (OC) cells and their exosomes using microarray data (accession number GSE103708) available from the Gene Expression Omnibus database, including exosomal samples from 13 OC cell lines and 3 normal ovarian surface epithelial cell lines, 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 target genes were analyzed using Database for Annotation, Visualization and Integrated Discovery and intersected with known OC-associated pathways downloaded from the Comparative Toxicogenomics Database. The associations between crucial miRNAs and target genes, and their clinical associations, were validated using data from The Cancer Genome Atlas. As a result, 16 upregulated and 6 downregulated DE-miRNAs were shared in OC cell lines and their exosomes compared with normal controls. The target genes of 11 common DE-miRNAs were predicted. Among these DE-miRNAs, a low expression of homosapiens (hsa)-miR-145-5p was significantly correlated with a poor prognosis and higher stages. Although 91 target genes were predicted for hsa-miR-145-5p, only 4 genes [connective tissue growth factor (CTGF), myotubularin-related protein 14, protein phosphatase 3 catalytic subunit alpha and suppressor of cytokine signaling 7] were suggested as risk factors for prognosis. The subsequent Pearson's correlation analysis validated a significant negative correlation between hsa-miR-145-5p and CTGF (r=-0.1126, P=0.02188). According to the results of the functional analysis, CTGF is involved in the Hippo signaling pathway (hsa04390). In conclusion, decreased expression of hsa-miR-145 in OC and OC-derived exosomes may be a crucial biomarker for the diagnosis and treatment of OC.