Academic Journal
miR-449, identified through antiandrogen exposure, mitigates functional biomarkers associated with ovarian cancer risk
| Title: | miR-449, identified through antiandrogen exposure, mitigates functional biomarkers associated with ovarian cancer risk |
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| Authors: | Xia Wang, Ho-Hyung Woo, Michelle Wei, Steven Gibson, Mitzi Miranda, Demaretta Rush, Janiel Cragun, Wenxin Zheng, Guang Yao, Setsuko K. Chambers |
| Source: | Scientific Reports, Vol 14, Iss 1, Pp 1-12 (2024) |
| Publisher Information: | Nature Portfolio, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | MicroRNA, CSF1R, Androgen receptor, Flutamide, Ovarian cancer risk, Medicine, Science |
| More Details: | Abstract The involvement of the androgen receptor (AR) pathway in developing epithelial ovarian cancer is increasingly acknowledged. However, the specific mechanisms by which anti-androgen agents, such as flutamide, may prevent ovarian cancer and their efficacy remain unknown. This study was initiated by investigating the impact of flutamide on miRNA expression in women at high risk (HR) for ovarian cancer. Ovarian and tubal tissues, free from ovarian, tubal, peritoneal cancers, and serous tubal intraepithelial carcinoma (STIC), were collected from untreated and flutamide-treated HR women as well as low-risk (LR) women controls. We performed miRNA sequencing on these 3 sample cohorts and observed that flutamide normalized miRNA levels in HR tissues, notably upregulating the miR-449 family to levels seen in LR tissues. In subsequent tests in primary ovarian epithelial cells and ovarian cancer cell lines (SKOV3 and Hey), flutamide also increased miR-449a and miR-449b-5p levels. Introducing mimics of these miRNAs reduced the mRNA and protein levels of AR and colony-stimulating factor 1 receptor (CSF1R, also known as c-fms), both of which are known contributors to ovarian cancer progression, with emerging evidence also supporting their roles in ovarian cancer initiation. Ovarian cancer cell migration was inhibited upon introducing miR-449a and miR-449b-5p mimics. Together, our study suggests a novel dual-inhibitory mechanism of flutamide on the AR pathway (AR expression suppression in addition to direct androgen antagonism) and supports its chemopreventive potential in ovarian cancer, especially for HR patients with low miR-449 expression. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-80173-z |
| Access URL: | https://doaj.org/article/1b9cc834ec814382a6f610737feaff87 |
| Accession Number: | edsdoj.1b9cc834ec814382a6f610737feaff87 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-024-80173-z |
| Published in: | Scientific Reports |
| Language: | English |