Reproductive biomedicine online, 2016-04, Vol.32 (4), p.434-445
2016
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4
- Ist Teil von
- Reproductive biomedicine online, 2016-04, Vol.32 (4), p.434-445
- Ort / Verlag
- Netherlands: Elsevier Ltd
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Abstract 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1472-6483eISSN: 1472-6491DOI: 10.1016/j.rbmo.2015.12.013Titel-ID: cdi_proquest_miscellaneous_1779441631
- Format
- –
- Schlagworte
- Cell Line, Cell Movement - genetics, Cell Proliferation - genetics, Down-Regulation, EMT, endometriosis, Endometriosis - genetics, Endometriosis - pathology, Female, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, Homeodomain Proteins - physiology, Humans, Kruppel-Like Transcription Factors - genetics, Kruppel-Like Transcription Factors - metabolism, Kruppel-Like Transcription Factors - physiology, microRNA, MicroRNAs - physiology, miR-200b, Obstetrics and Gynecology, Repressor Proteins - genetics, Repressor Proteins - metabolism, Repressor Proteins - physiology, stem cells, Stromal Cells - metabolism, subfertility, Up-Regulation, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1 - genetics, Zinc Finger E-box-Binding Homeobox 1 - metabolism, Zinc Finger E-box-Binding Homeobox 1 - physiology