Abstract | BACKGROUND: METHODS: Assays of cell viability, proliferation, migration, apoptosis, and colony formation were performed to investigate the pro- tumorigenesis effect of NET and the effects of miR-181a on human breast epithelial MCF10A cells. The expressions of cell-proliferation-related genes and apoptotic factors were analyzed by quantitative RT-PCR and Western blot in MCF10A cells treated with NET and miR-181a. RESULTS: NET significantly increased MCF10A cell viability, proliferation, migration, and colony formation, but reduced cellular apoptosis. In addition, NET increased the expression of progesterone receptor membrane component 1 (PGRMC1), EGFR, B-cell lymphoma 2, cyclin D1, and proliferating cell nuclear antigen, but decreased the expression of pro-apoptosis factors, such as Bax, caspase-7, and caspase-9. Overexpression of miR-181a strongly inhibited the effects of NET on MCF10A cells and abrogated NET-stimulated PGRMC1, EGFR, and mTOR expression. CONCLUSIONS: Activation of the PGRMC1/EGFR-PI3K/Akt/mTOR signaling pathway is the primary mechanism underlying the pro- tumorigenesis effects of NET on human breast epithelial MCF10A cells. Additionally, miR-181a can suppress the effects of NET on these cells. These data suggest a therapeutic potential for miR-181a in reducing or preventing the risk of breast cancer in hormone replacement therapy using NET.
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Authors | Guiju Cai, Yuejiao Wang, Tahiri Houda, Chun Yang, Lijuan Wang, Muqing Gu, Alfred Mueck, Stephane Croteau, Xiangyan Ruan, Pierre Hardy |
Journal | Translational oncology
(Transl Oncol)
Vol. 14
Issue 6
Pg. 101068
(Jun 2021)
ISSN: 1936-5233 [Print] United States |
PMID | 33730679
(Publication Type: Journal Article)
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Copyright | Copyright © 2021. Published by Elsevier Inc. |