MiR-183 Regulates ITGB1P Expression and Promotes Invasion of Endometrial Stromal Cells

Abstract

We applied in the previous study miRNA microarray screening analysis to identify several differentially expressed miRNAs, including miR-183 in normal, eutopic, and ectopic endometrium. Knockdown of miR-183 expression induced the invasiveness and inhibition of apoptosis in endometrial stromal cells. The current study aims to identify the miR-183 targets with relevance to cell functions in endometrial stromal cells, to verify the interaction of miR-183 with its target genes, and to confirm the role of miR-183 in the process of endometriosis. Using microarray analysis, we identified 27 differentially expressed genes (19 were upregulated and 8 downregulated), from which we selected 4 downregulated genes (ITGB1, AMIGO2, VAV3, and PSEN2) based on GO databases for functional analysis and significant pathway analysis. Western blotting analyses showed that integrin β1 (ITGB1), but not AMIGO2, was affected by miR-183 overexpression, whereas no protein expression of VAV3 and PSEN2 was detected. Luciferase reporter assay verified that ITGB1 is a target gene of miR-183. Moreover, we found that ITGB1 is overexpressed in the endometrium of endometriosis patients. Furthermore, overexpression of ITGB1 rescued the repressive effects of miR-183 on the invasiveness of endometrial stromal cells. These findings, together with the fact that ITGB1 is a critical factor for cell adhesion and invasiveness, suggest that miR-183 may be involved in the development of endometriosis by regulating ITGB1 in endometrial stromal cells.

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

“…Several integrins, including αvβ3, αvβ5, αvβ6, α4β1, and α6β1, have been reported to mediate the attachment of endometrial cells to the mesothelium ( 4 , 34 – 36 ). The expression of these integrins is tightly regulated by diverse molecules, such as interleukin (IL)-1, IL-8, macrophage inhibitory factor (MiR)-183, prostaglandin E2, and a cannabinoid receptor agonist ( 7 , 9 – 11 , 37 , 38 ). However, despite the obvious importance of TGF-β1 in the progression of endometriosis ( 13 , 17 ), there have been no reports of the TGF-β1 function in the regulation of integrins in endometrial cells.…”

miR-182 aids in receptive endometrium development in dairy goats by down-regulating PTN expression

“…Functional studies indicated that miR-183 might contribute to human endometrial stromal cell apoptosis and impose a negative regulatory impact on cell invasiveness in humans [67]. In addition, miR-21 is highly expressed in the sub-luminal ESC cells at implantation sites is regulated in active blastocysts in the mouse [68].…”

hTERT mediates gastric cancer metastasis partially through the indirect targeting of ITGB1 by microRNA-29a

“…The expression level of hTERT was positively correlated with ITGB1 expression in clinical GC specimens, which was in accordance with the results from the proteomic analysis. Many studies have reported that ITGB1 could be regulated by microRNAs 23 24 , we then developed the hypothesis that whether hTERT could regulate ITGB1 via microRNAs.…”