MiR-205 promotes motility of ovarian cancer cells via targeting ZEB1.
OBJECTIVE
To investigate the clinical significance of microRNA-205 (miR-205) and zinc finger E-box binding homeobox 1 (ZEB1) in epithelial ovarian cancer (EOC) and the underlying mechanisms by which they are involved into tumorigenesis.


METHODS
Expression levels of miR-205 and ZEB1 mRNA in EOC tissues were detected by quantitative real-time PCR. Their associations with clinicopathological features of EOC patients were statistically analyzed. Luciferase reporter assay was used to confirm target associations between miR-205 and ZEB1. After that, the functions of miR-205-ZEB1 axis on cell migration and invasion were further determined by transwell assay in vitro.


RESULTS
Expression levels of miR-205 (P=0.0001) and ZEB1 mRNA (P<0.0001) in clinical EOC tissues were significantly higher and lower than those in normal tissues, respectively. Interestingly, there was a negative correlation between miR-205 and ZEB1 mRNA expression in EOC tissues (P=0.01). Additionally, miR-205-upregulation and/or ZEB1-downregulation were significantly associated with high pathological grade and advanced clinical stage of EOC patients (all P<0.05). Meantime, luciferase reporter assays identified ZEB1 as a direct target of miR-205 in EOC cells. Moreover, miR-205 blockage inhibited, whereas miR-205 mimics promoted the motility of EOC cells in vitro. Importantly, all the alterations of the above cellular phenotypes by blocking or enhancing of miR-205 could be alleviated by subsequent suppression or re-introduction of its target ZEB1, respectively.


CONCLUSIONS
MiR-205, acting as an oncogenic miRNA, may promote the clinical progression of EOC patients and enhance the cellular motility in vitro by directly and negatively regulating ZEB1, providing a potential therapeutic strategy for suppression of EOC metastasis.
Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
Ke
K
Niu
Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
Wenjie
W
Shen
Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
Yinghui
Y
Zhang
Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
Ying
Y
Zhao
Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China. Electronic address: yongx_lu@163.com.
Yongxian
Y
Lu
D000328:Adult; D000077216:Carcinoma, Ovarian Epithelial; D002465:Cell Movement / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors; D000071799:Zinc Finger E-box-Binding Homeobox 1; C534425:MIR205, human; C486307:ZEB1 protein, human
Epithelial ovarian cancer; Invasion; MicroRNA-205; Migration; Zinc finger E-box binding homeobox 1