Open Access

ARTICLE

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

QIAOLING WU^1,2, ZHAOLEI CUI³, HONGMEI XIA¹, SHAN JIANG¹, JING BAI⁴, ZHUO SHAO⁴, YANG SUN^1,*

1 Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
2 Department of Gynecology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
3 Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
4 Geneplus-Beijing Institute, Beijing, China

* Corresponding Author: YANG SUN. Email:

BIOCELL 2023, 47(5), 1039-1050. https://doi.org/10.32604/biocell.2023.027494

Received 01 November 2022; Accepted 02 February 2023; Issue published 10 April 2023

Abstract

Background: Ovarian cancer (OC) is a leading cause of gynecological cancer-linked deaths worldwide. Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A (CLEC5A) are associated with tumorigenesis in cancers that was further probed. Methods: Exosomal miR-1825 expression in exosomes and its impact on overall survival (OS) prediction were determined using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data. Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves. The CLEC5A expression pattern in OC was validated using immunohistochemistry. The CIBERSORT algorithm was used to compare the immune cell landscape, and the results were validated in a GEO cohort. Finally, the predicted half maximal inhibitory concentration (IC50) values for five commonly used chemotherapy agents were also compared. Results: MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor. The CLEC5A gene was found to be a target of miR-1825, the upregulation of which was correlated with a poor prognosis. M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group, while T follicular helper cell infiltration was reduced in it. While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group, that of docetaxel, gemcitabine, and paclitaxel was lower. Conclusion: MiR-1825, a promising OC biomarker, may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.

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