Ke Niu1, Wenjie Shen1, Yinghui Zhang1, Ying Zhao1, Yongxian Lu2. 1. Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China. 2. Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China. Electronic address: yongx_lu@163.com.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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. CONCLUSION: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.
Authors: Aritro Nath; Eunice Y T Lau; Adam M Lee; Paul Geeleher; William C S Cho; R Stephanie Huang Journal: Proc Natl Acad Sci U S A Date: 2019-09-23 Impact factor: 11.205