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.
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Authors | Shaoru Li, Ruili Hu, Chuanhong Wang, Fang Guo, Xiaoli Li, Shijin Wang |
Journal | Molecular medicine reports
(Mol Med Rep)
Vol. 9
Issue 6
Pg. 2393-9
(Jun 2014)
ISSN: 1791-3004 [Electronic] Greece |
PMID | 24715036
(Publication Type: Journal Article, Retracted Publication)
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Chemical References |
- Estrogen Receptor alpha
- MIRN22 microRNA, human
- MicroRNAs
- Cyclin D1
- Estradiol
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Topics |
- Carcinoma, Endometrioid
(genetics, metabolism, pathology)
- Cell Cycle
(drug effects, genetics)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclin D1
(metabolism)
- Estradiol
(pharmacology)
- Estrogen Receptor alpha
(genetics, metabolism)
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- MicroRNAs
(genetics)
- Neoplasm Invasiveness
- Ovarian Neoplasms
(genetics, metabolism, pathology)
- Signal Transduction
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