A extracellular secretion of miR-1825 wrapped by exosomes increases CLEC5A expression: a potential oncogenic mechanism in ovarian cancer

Abstract

Background: Ovarian cancer (OC) is an important cause of gynecologic cancer-related mortality worldwide. Exosomal miR-1825 and its target gene CLEC5A have been shown to have a significant association with tumorigenesis in other cancers. Methods: Exosomal miR-1825 expression and its ability in overall survival(OS) prediction were determined using GEO and TCGA data. Target genes of miR-1825 were searched in five prediction databases, and differentially expressed prognostic genes were identified. We performed GO and KEGG enrichment analyses. The ability of CLEC5A in OS prediction was assessed using univariate and multivariate Cox regression and Kaplan-Meier curves. Immunohistochemistry was applied to validate the CLEC5A expression pattern in OC. The immune cell landscape was compared using the CIBERSORT algorithm, and the results were validated in a GEO cohort. Finally, the predicted IC50 of five common chemotherapy agents was compared. Results: MiR-1825 was elevated in exosomes derived from OC cells and served as a tumor suppressor. The CLEC5A gene was confirmed as a target of miR-1825, whose upregulation was correlated with a poor prognosis. M2 macrophage infiltration was significantly enhanced in CLEC5A high expression group, and T follicular helper cell infiltration was reduced in it. The predicted IC50 for cisplatin and doxorubicin was higher in CLEC5A high expression group, and that for docetaxel, gemcitabine, and paclitaxel was lower. Conclusion: MiR-1825 may promote OC progression by increasing CLEC5A expression through exosome-mediated efflux from tumor cells and could be a promising biomarker for OC.