Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China; Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
Maturitas. 2018 Aug;114:60-66. doi: 10.1016/j.maturitas.2018.06.004. Epub 2018 Jun 5.
Recent investigations have indicated that hormone therapy may increase the risk of breast cancer (BC), and the addition of synthetic progestins may play a critical role in this. Several studies have pointed out the important role of progesterone receptor membrane component 1 (PGRMC1) in the development of BC, especially with hormone therapy using progestins. Although the deregulation of microRNA-181a (miR-181a) is often associated with human BC, the effect of miR-181a on PGRMC1 expression during hormone therapy has not been investigated.
Cell viability assay and apoptosis assay were performed to investigate the pro-BC effect of progestin (norethisterone, NET) and anti-BC effect of miR-181a on MCF-7 cells. Quantitative RT-PCR and Western blot analysis were used to evaluate gene expressions in the NET-treated MCF-7 cells.
NET dose-dependently increased BC cell viability and this effect was accompanied by increased expression of PGRMC1. Overexpression of miR-181a strongly reduced the cell viability of MCF-7 cells, mainly through increased apoptosis, which was evidenced by substantially increased gene expression of pro-apoptosis factors such as BAX and CASPASE 9 in miR-181a overexpressed cells. Importantly, miR-181a abrogated NET-stimulated cell viability and PGRMC1 expression.
We provide evidence that miR-181a promotes MCF-7 cell apoptosis. Moreover, miR-181a suppressed NET-provoked cell viability and PGRMC1 expression in MCF-7 cells. These data may suggest a therapeutic strategy of using miR-181a to reduce BC risk in progestin hormone replacement therapy.
最近的研究表明，激素疗法可能会增加乳腺癌（BC）的风险，而合成孕激素的添加可能在此过程中发挥关键作用。几项研究指出，孕激素受体膜成分 1（PGRMC1）在 BC 的发展中起着重要作用，特别是在使用孕激素的激素疗法中。虽然 microRNA-181a（miR-181a）的失调通常与人类 BC 有关，但 miR-181a 对激素治疗中 PGRMC1 表达的影响尚未得到研究。
通过细胞活力测定和细胞凋亡测定来研究孕激素（炔诺酮，NET）对 MCF-7 细胞的促癌作用和 miR-181a 的抗 BC 作用。定量 RT-PCR 和 Western blot 分析用于评估 NET 处理的 MCF-7 细胞中的基因表达。
NET 呈剂量依赖性地增加 BC 细胞活力，并且这种作用伴随着 PGRMC1 表达的增加。miR-181a 的过表达强烈降低 MCF-7 细胞的活力，主要是通过增加凋亡来实现的，这可以通过 miR-181a 过表达细胞中促凋亡因子如 BAX 和 CASPASE 9 的基因表达明显增加来证明。重要的是，miR-181a 阻断了 NET 刺激的细胞活力和 PGRMC1 表达。
我们提供了证据表明 miR-181a 促进 MCF-7 细胞凋亡。此外，miR-181a 抑制了 NET 引起的 MCF-7 细胞活力和 PGRMC1 表达。这些数据可能提示了一种使用 miR-181a 减少孕激素激素替代疗法中 BC 风险的治疗策略。
