GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression.
Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PCa tissues and cell lines. Downregulation of miR-503 was strongly associated with aggressive clinical-pathological features and poor prognosis in PCa patients. Ectopic expression of miR-503 significantly inhibited tumor cells growth, cell migration and invasion in vitro and in vivo. Mechanistic studies revealed that ZNF217 was a direct target downstream target of miR-503. Knockdown of ZNF217 mimicked the tumor-suppressive effects of miR-503 overexpression on PCa invasion, whereas ZNF217 overexpression attenuated the tumor-suppressive function of miR-503. Subsequently, miR-503 further modulated the activation of ZNF217-downstream epithelial-mesenchymal transition (EMT) genes. Besides, we also found that GATA3 directly increased miR-503 expression and thus decreased ZNF217 expression, indicating the involvement of GATA3/miR-503/ZNF217 signaling in EMT process. Collectively, our results demonstrated that GATA3-driven expression of miR-503 inhibits PCa progression by repressing ZNF217 expression, and also implicated the potential application of miR-503 in PCa therapy.
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
Xingkang
X
Jiang
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
Yue
Y
Chen
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
E
E
Du
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
Kuo
K
Yang
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
Zhihong
Z
Zhang
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China. Electronic address: yongshiqi@126.com.
Shiyong
S
Qi
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China. Electronic address: yongxu2012@yahoo.com.
Yong
Y
Xu
D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011485:Protein Binding / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C545473:MIRN503 microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; C113698:ZNF217 protein, human
GATA3; Prostate cancer; ZNF217; miR-503; microRNA