Reduced Expression of Eukaryotic Translation Initiation Factor 3 Subunit e and Its Possible Involvement in the Epithelial-Mesenchymal Transition in Endometriosis

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This study found reduced expression of eIF3e and E-cadherin but increased expression of TGF-β1, Snail, and vimentin in ectopic endometrial cells from women with endometriosis, suggesting eIF3e downregulation may contribute to epithelial-mesenchymal transition.

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This study investigated whether reduced expression of the eukaryotic translation initiation factor 3 subunit e (eIF3e) is involved in epithelial-mesenchymal transition (EMT) in ovarian endometriosis by comparing immunohistochemistry markers in ectopic endometriotic tissue from 40 premenopausal women with laparoscopically and histologically diagnosed ovarian endometriomas to age- and menstrual phase-matched endometrium from 40 controls without endometriosis, adenomyosis, or fibroids. Endometriotic epithelial cells showed significantly reduced eIF3e immunoreactivity and E-cadherin, with increased TGF-β1, Snail, vimentin, and PCNA, and eIF3e levels correlated negatively with TGF-β1 and Snail and positively with E-cadherin. A key limitation is that the work is correlative at the protein expression level and the proposed mechanism (preferential Snail translation) is not directly tested. This paper is centrally about endometriosis — it focuses on eIF3e downregulation as a potential contributor to EMT in ovarian endometriomas.

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Abstract

Epithelial-mesenchymal transition (EMT) is now well documented to be involved in the development of endometriosis through the promotion of invasion and fibrogenesis. To date, several factors have been reported to be involved in EMT in endometriosis. The eukaryotic translation initiation factor 3 subunit e (eIF3e) protein is a component of the multisubunit eIF3 complex essential for cap-dependent translation initiation. The aim of this study was to investigate whether eIF3e is involved in EMT in endometriosis. We recruited 40 premenopausal women (34.7 [6.8] years) with laparoscopically and histologically diagnosed ovarian endometriomas, and their ectopic endometrial tissue samples were collected after informed consent. As controls, endometrial tissue samples were obtained after informed consent from 40 premenopausal women, roughly age-matched (36.9 [6.4] years) and menstrual phase-matched with endometriosis group, who underwent surgery for benign gynecologic disorders or cervical intraepithelial neoplasia but without endometriosis, adenomyosis, or uterine fibroids. All tissue samples were subjected to immunohistochemistry analysis of eIF3e, transforming growth factor (TGF-β1), Snail, E-cadherin, vimentin, and proliferating cell nuclear antigen (PCNA). We found significantly reduced immunoreactivity against eIF3e and E-cadherin but elevated immunoreactivity against TGF-β1, Snail, vimentin, and PCNA in endometriotic epithelial cells when compared to that of control endometrium (all P values <.05). The eIF3e staining levels correlated negatively with that of TGF-β1 and Snail but positively with that of E-cadherin (all P values <.05). These data suggest that eIF3e downregulation may be involved in EMT in endometriosis, possibly through preferential translation of Snail. Future studies are warranted to confirm whether this is the mechanism.
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Abstract

Epithelial-mesenchymal transition (EMT) is now well documented to be involved in the development of endometriosis through the promotion of invasion and fibrogenesis. To date, several factors have been reported to be involved in EMT in endometriosis. The eukaryotic translation initiation factor 3 subunit e (eIF3e) protein is a component of the multisubunit eIF3 complex essential for cap-dependent translation initiation. The aim of this study was to investigate whether eIF3e is involved in EMT in endome-triosis. We recruited 40 premenopausal women (34.7 [6.8] years) with laparoscopically and histologically diagnosed ovarian endometriomas, and their ectopic endometrial tissue samples were collected after informed consent. As controls, endometrial tissue samples were obtained after informed consent from 40 premenopausal women, roughly age-matched (36.9 [6.4] years) and menstrual phase-matched with endometriosis group, who underwent surgery for benign gynecologic disorders or cervical intraepithelial neoplasia but without endometriosis, adenomyosis, or uterine fibroids. All tissue samples were subjected to immunohistochemistry analysis of eIF3e, transforming growth factor (TGF-b1), Snail, E-cadherin, vimentin, and proliferating cell nuclear antigen (PCNA). We found significantly reduced immunoreactivity against eIF3e and E-cadherin but elevated immu-noreactivity against TGF-b1, Snail, vimentin, and PCNA in endometriotic epithelial cells when compared to that of control endometrium (all P values <.05). The eIF3e staining levels correlated negatively with that of TGF-b1 and Snail but positively with that of E-cadherin (all P values <.05). These data suggest that eIF3e downregulation may be involved in EMT in endometriosis, possibly through preferential translation of Snail. Future studies are warranted to confirm whether this is the mechanism. Similar content being viewed by others

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endometriosisadenomyosis

MeSH descriptors

Endometriosis Endometrium Epithelial-Mesenchymal Transition Eukaryotic Initiation Factor-3 Adult Cadherins Cadherins Endometriosis Endometrium Epithelial-Mesenchymal Transition Eukaryotic Initiation Factor-3 Female Humans Middle Aged Snail Family Transcription Factors Snail Family Transcription Factors Transforming Growth Factor beta1 Transforming Growth Factor beta1 Vimentin Vimentin

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