microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4

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• 作者：Julia C. Eggers^a ; Valentina Martino^b ; Rolland Reinbold^b ; Sebastian D. Schä ; fer^a ; Ludwig Kiesel^a ; Anna Starzinski-Powitz^c ; Andreas N. Schü ; ring^a ; Bjö ; rn Kemper^d ; Burkhard Greve^e ; ¹ ; ^{greveb@uni-muenster.de" class="auth_mail" title="E-mail the corresponding author} ; Martin Gö ; tte^a ; ¹ ; ^{mgotte@uni-muenster.de" class="auth_mail" title="E-mail the corresponding author}Author Vitae
• 关键词：EMT ; endometriosis ; microRNA ; miR-200b ; stem cells ; subfertility
• 刊名：Reproductive BioMedicine Online
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：32
• 期：4
• 页码：434-445
• 全文大小：2030 K

文摘

Endometriosis is characterized by growth of endometrial tissue at ectopic locations. Down-regulation of microRNA miR-200b is observed in endometriosis and malignant disease, driving tumour cells towards an invasive state by enhancing epithelial-to-mesenchymal transition (EMT). miR-200b up-regulation may inhibit EMT and invasive growth in endometriosis. To study its functional impact on the immortalized endometriotic cell line 12Z, the stromal cell line ST-T1b, and primary endometriotic stroma cells, a transient transfection approach with microRNA precursors was employed. Expression of bioinformatically predicted targets of miR-200b was analysed by qPCR. The cellular phenotype was monitored by Matrigel invasion assays, digital-holographic video microscopy and flow cytometry. qPCR revealed significant down-regulation of ZEB1 (P < 0.05) and ZEB2 (P < 0.01) and an increase in E-cadherin (P < 0.01). miR-200b overexpression decreased invasiveness (P < 0.0001) and cell motility (P < 0.05). In contrast, cell proliferation (P < 0.0001) and the stemness-associated side population phenotype (P < 0.01) were enhanced following miR-200b transfection. These properties were possibly due to up-regulation of the pluripotency-associated transcription factor KLF4 (P < 0.05) and require attention when considering therapeutic strategies. In conclusion, up-regulation of miR-200b reverts EMT, emerging as a potential therapeutic approach to inhibit endometriotic cell motility and invasiveness.