miR-22 inhibits proliferation and invasion in estrogen receptor α-positive endometrial endometrioid carcinomas cells.
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.
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Shaoru
S
Li
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Ruili
R
Hu
Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Zhengzhou City, Zhengzhou, Henan 450012, P.R. China.
Chuanhong
C
Wang
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Fang
F
Guo
Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Fangcheng County, Nanyang, Henan 473200, P.R. China.
Xiaoli
X
Li
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Shijin
S
Wang
D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
D047628:Estrogen Receptor alpha; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D004958:Estradiol