The Department of Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
The Department of Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Life Sci. 2020 Feb 1;242:117190. doi: 10.1016/j.lfs.2019.117190. Epub 2019 Dec 18.
The alteration of PTEN expression may be a vital part of the pathological and physiological mechanisms in infertility-related with endometriosis. However, the potential mechanisms underlying abnormal expression of PTEN and its role in progesterone-resistant endometriosis have not been thoroughly elucidated. In this study, our data showed the PTEN messenger RNA (mRNA) level and protein expression was reduced in progesterone-resistant endometriosis tissue and primary stomal cells. Low levels of PTEN in endometrial stromal cells led to higher cell proliferation and resistance to progesterone. In terms of PTEN suppression in progesterone-resistant endometriosis, the mRNA level of miR-92a was correlated negatively with PTEN level. Transfection of miR-92a mimic reduced PTEN expression and made the stromal cells more resistant to progesterone treatment. Inhibition of miR-92a by its antagomir had the opposite effects. Results of the luciferase reporter assay for the 3'-nontranslated region suggested that miR-92a directly modulated PTEN levels. Moreover, miR-92a inhibition by its antagomir enhanced the therapeutic effect of progesterone, which suppressed stromal cell proliferation, and reduced the formation of ectopic lesions in the mouse model of endometriosis. Hence, this study revealed that miR-92a contributed to the development of progesterone resistant endometriosis by suppression of PTEN expression, and modulation of miR-92a might be a potential medical method of treating endometriosis.
PTEN 表达的改变可能是与子宫内膜异位症相关的不孕病理和生理机制的重要组成部分。然而，PTEN 异常表达的潜在机制及其在孕激素抵抗性子宫内膜异位症中的作用尚未得到充分阐明。在这项研究中，我们的数据显示，孕激素抵抗性子宫内膜异位症组织和原代腔上皮细胞中 PTEN 的信使 RNA(mRNA)水平和蛋白表达降低。子宫内膜间质细胞中 PTEN 水平较低导致细胞增殖增加和对孕激素的抵抗。在孕激素抵抗性子宫内膜异位症中抑制 PTEN 方面，miR-92a 的 mRNA 水平与 PTEN 水平呈负相关。转染 miR-92a 模拟物降低了 PTEN 表达，使基质细胞对孕激素治疗更具抵抗力。miR-92a 拮抗剂的抑制作用则相反。3'非翻译区的荧光素酶报告基因检测结果表明，miR-92a 可直接调节 PTEN 水平。此外，miR-92a 拮抗剂抑制 miR-92a 增强了孕激素的治疗效果，抑制了基质细胞增殖，并减少了子宫内膜异位症小鼠模型中异位病变的形成。因此，本研究表明，miR-92a 通过抑制 PTEN 表达促进孕激素抵抗性子宫内膜异位症的发展，调节 miR-92a 可能是治疗子宫内膜异位症的一种潜在医学方法。
