CPEB3, an RNA-Binding Protein, Modulates the Behavior of Endometriosis-Derived Stromal Cells via Regulating CXCL12

Endometriosis is a benign gynecological disease sharing several features with malignant tumor. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a potential target of miR-21-5p, is downregulated in endometriotic specimens. However, the function of CPEB3 in endometriosis is elusive. In this study, in cultured primary human endometrial stromal cells (ESCs), the overexpression and inhibition of CPEB3 were achieved by transduction of adenovirus-mediated CPEB3 overexpressed plasmid and shRNA, respectively. Functional analysis uncovered that upregulated CPEB3 reduced cell viability and arrested cell cycle entry. The expression of cyclin D1 and c-Myc was decreased after CPEB3 overexpression. Overexpression of CPEB3 facilitated ESC apoptotic potential, accompanied by increased Bax, cleaved-caspase 3 and cleaved-caspase 9, and reduced Bcl2. Moreover, elevated CPEB3 weakened migration and invasion abilities of ESCs. CPEB3 overexpression also reduced the expression of fibronectin and vimentin and the activities of matrix metalloproteinase (MMP)-9 and MMP-2. Interestingly, these effects were counteracted by CPEB3 inhibition. Furthermore, CPEB3 controlled the protein level of CXCL12, a homeostatic chemokine. CXCL12 elevation partially reversed the effects of CPEB3 on inhibiting ESC proliferation, migration and invasion, and promoting apoptosis. Based on these findings, it seems possible that CPEB3, as a critical player, attenuated the progression of endometriosis through repressing CXCL12 expression.

Automated summary

This study reveals the role of CPEB3 in endometriosis. CPEB3 can attenuate the progression of endometriosis by repressing CXCL12 expression, and it affects cell viability, cell cycle entry, cell apoptosis, cell migration and invasion, and extracellular matrix degradation.