MiR-22 inhibits proliferation and invasion in estrogen receptor α-positive endometrial endometrioid carcinomas cells

Abstract

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.