miR-573 inhibits prostate cancer metastasis by regulating epithelialmesenchymal transition

Lin Wang, Guanhua Song, Weiwei Tan, Mei Qi, Lili Zhang, Jonathan Chan, Jindan Yu, Jinxiang Han, Bo Han*

*Corresponding author for this work

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The metastastic cascade is a complex process that is regulated at multiple levels in prostate cancer (PCa). Recent evidence suggests that microRNAs (miRNAs) are involved in PCa metastasis and hold great promise as therapeutic targets. In this study, we found that miR-573 expression is significantly lower in metastatic tissues than matched primary PCa. Its downregulation is correlated with high Gleason score and cancer-related mortality of PCa patients (P = 0.041, Kaplan-Meier analysis). Through gain- and loss-of function experiments, we demonstrated that miR-573 inhibits PCa cell migration, invasion and TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro and lung metastasis in vivo. Mechanistically, miR573 directly targets the fibroblast growth factor receptor 1 (FGFR1) gene. Knockdown of FGFR1 phenocopies the effects of miR-573 expression on PCa cell invasion, whereas overexpression of FGFR1 partially attenuates the functions of miR-573. Consequently, miR-573 modulates the activation of FGFR1-downstream signaling in response to fibroblast growth factor 2 (FGF2). Importantly, we showed that GATA3 directly increases miR-573 expression, and thus down-regulates FGFR1 expression, EMT and invasion of PCa cells in a miR-573-dependent manner, supporting the involvement of GATA3, miR-573 and FGFR1 in controlling the EMT process during PCa metastasis. Altogether, our findings demonstrate a novel mechanism by which miR-573 modulates EMT and metastasis of PCa cells, and suggest miR-573 as a potential biomarker and/ or therapeutic target for PCa management.

Original languageEnglish (US)
Pages (from-to)35978-35990
Number of pages13
JournalOncotarget
Volume6
Issue number34
DOIs
StatePublished - Jan 1 2015

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Keywords

  • FGFR1
  • GATA3
  • Metastasis
  • MiR-573
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Wang, L., Song, G., Tan, W., Qi, M., Zhang, L., Chan, J., Yu, J., Han, J., & Han, B. (2015). miR-573 inhibits prostate cancer metastasis by regulating epithelialmesenchymal transition. Oncotarget, 6(34), 35978-35990. https://doi.org/10.18632/oncotarget.5427