Different Progestins Alter Transcriptional Expression of primiR-190 and primiR-199a-1 in T47D Breast Cancer Cells

Background: Breast cancer accounts for 30% of all new cancers diagnosed in women annually. Current evidence shows that 70-80% of newly diagnosed breast cancers are hormone sensitive, indicating that their growth is promoted by hormones such as progestins and estrogens. Progestins have been found to alter microRNA expression in cancer and various tissues in humans, potentially contributing to breast cancer progression and metastasis. Different progestins regulate specific microRNAs known to influence genes that promote cancer development and growth. Our initial computer-based analysis identified primiR-190 and primiR-199a-1 as potential targets for CD44 and vascular endothelial growth factor (VEGF), proteins essential in breast cancer growth. This study determined the effect of different progestins on transcriptional expression of primiR-190 and primiR-199a-1 in T47D breast cancer cells. Methods: Progesterone receptor (PR)-positive T47D breast cancer cells were exposed to the natural hormone, progesterone, and three synthetic progestins, medroxyprogesterone acetate, norgesterol, and norethindrone for 24 hours. Real-time PCR was used to determine the transcriptional expression of primiR-190 and primiR-199a-1. To confirm the role of PR-dependent pathways on expression of both primiR-190 and primiR-199a-1, we also tested the different progestins on a progesterone receptor (PR) negative cell line, T47Dco-Y. Results: Our results showed significantly increased transcriptional expression of primiR-190 and primiR-199a-1 in T47D breast cancer cells when exposed to progesterone and synthetic progestins. RU-486, a PR antagonist, suppressed progestin-induced expression of both primiR-190 and primiR-199a-1. We did not observe progestin-induced effects in the PR-negative cell line. These results suggest a direct involvement of PR-dependent pathways in regulation of these two microRNAs. This study also found no effect on expression of primiR-190 and primiR-199a-1 when T47D cells were exposed to 17β estradiol and DMSO providing further evidence that progestins exclusively regulate expression of these two microRNAs. Conclusion: We concluded that different progestins significantly increase transcriptional expression of primiR-190 and primiR-199a-1 through progesterone receptor-mediated pathways. Our results indicate that primiR-190 and primiR-199a-1 expression can be useful as biomarkers in some forms of PR-positive breast cancers. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.