Li Shaoru, Hu Ruili, Wang Chuanhong, Guo Fang, Li Xiaoli, Wang Shijin
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Zhengzhou City, Zhengzhou, Henan 450012, P.R. China.
Mol Med Rep. 2014 Jun;9(6):2393-9. doi: 10.3892/mmr.2014.2123. Epub 2014 Apr 8.
Endometrial endometrioid carcinomas (EECs) account for >80% of endometrial carcinomas (ECs). Continuous stimulation of the endometrium by estrogen is a risk factor for the tumorigenesis of estrogen receptor (ER) α-positive EEC. MicroRNA-22 (miR-22) has been reported to be implicated in the regulation of various types of cancer and directly targets ERα. However, an exact regulatory mechanism between miR-22 and ERα in EEC has yet to be investigated. To the best of our knowledge, the present study demonstrated for the first time that the expression of miR-22 was significantly downregulated in ERα-positive EEC tissues and cell lines, RL95-2 and Ishikawa, when compared with that in normal endometrium and ERα-negative EEC samples. This indicated that miR-22 may be important in ERα-positive EEC, possibly through an estrogen-dependent mechanism. miR-22 mimics were then transfected into RL95-2 and Ishikawa cells, respectively, and revealed that the introduction of miR-22 markedly downregulated the mRNA and protein levels of ERα. Further investigation demonstrated that miR-22 was able to effectively reverse 17β-estradiol (E2)‑induced cell proliferation, cell cycle progression and invasion of ERα-positive RL95-2 and Ishikawa cells, at least partially through inhibiting the expression of Cyclin D1 as well as the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. In conclusion, the present study, to the best of our knowledge, was the first to reveal an inhibitory role of miR-22 in ERα-positive EEC tissues and cells, indicating that miR-22 may be a novel candidate for the endocrine therapy of ERα-positive EEC.
子宫内膜样腺癌（EEC）占子宫内膜癌（EC）的80%以上。雌激素对子宫内膜的持续刺激是雌激素受体（ER）α阳性EEC发生肿瘤的危险因素。据报道，MicroRNA-22（miR-22）参与多种癌症的调控，并直接靶向ERα。然而，miR-22与ERα在EEC中的具体调控机制尚待研究。据我们所知，本研究首次证明，与正常子宫内膜和ERα阴性EEC样本相比，miR-22在ERα阳性EEC组织和细胞系RL95-2和Ishikawa中的表达显著下调。这表明miR-22在ERα阳性EEC中可能很重要，可能通过雌激素依赖机制发挥作用。随后，分别将miR-22模拟物转染到RL95-2和Ishikawa细胞中发现，导入miR-22可显著下调ERα的mRNA和蛋白水平。进一步研究表明，miR-22能够有效逆转17β-雌二醇（E2）诱导的ERα阳性RL95-2和Ishikawa细胞的增殖、细胞周期进程和侵袭，至少部分是通过抑制细胞周期蛋白D1的表达以及基质金属蛋白酶（MMP）-2和MMP-酶9的分泌来实现的。总之，据我们所知，本研究首次揭示了miR-22在ERα阳性EEC组织和细胞中的抑制作用，表明miR-22可能是ERα阳性EEC内分泌治疗的新候选药物。
