LEF1 targeting EMT in prostate cancer invasion is regulated by miR-34a

Jiaqian Liang, Yirong Li, Garrett Daniels, Karen Sfanos, Angelo De Marzo, Jianjun Wei, Xin Li, Wenqiang Chen, Jinhua Wang, Xuelin Zhong, Jonathan Melamed, Jun Zhao, Peng Lee

Research output: Contribution to journalArticle

Abstract

The microRNA-34a (miR-34a), a tumor-suppressive microRNA (miRNA), is implicated in epithelial-mesenchymal transition (EMT) and cancer stem cells. Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor in the Wnt signaling pathway, and has been suggested to be involved in regulation of cell proliferation and invasion. Here, the molecular mechanism of miR-34a and LEF1 in cooperatively regulating prostate cancer cell invasion is described. Molecular profiling analysis of miRNA levels in prostate cancer cells revealed a negative correlation between miR-34a and LEF1 expression, and the downregulation of LEF1 by miR-34a was confirmed by luciferase assays. Furthermore, miR-34a specifically repressed LEF1 expression through direct binding to its 30-untranslated regions (30-UTR). miR-34a modulated the levels of LEF1 to regulate EMT in prostate cancer cells. Functionally, miR-34a negatively correlated with the migration and invasion of prostate cancer cells through LEF1. An analysis of miR-34a expression levels in matched human tumor and benign tissues demonstrated consistent and statistically significant downregulation of miR-34a in primary prostate cancer specimens. These data strongly suggest that miR-34a/LEF1 regulation ofEMTplays an important role in prostate cancer migration and invasion.

Original languageEnglish (US)
Pages (from-to)681-688
Number of pages8
JournalMolecular Cancer Research
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2015

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Lymphoid Enhancer-Binding Factor 1
Epithelial-Mesenchymal Transition
MicroRNAs
Prostatic Neoplasms
Down-Regulation
Untranslated Regions
Wnt Signaling Pathway
Neoplastic Stem Cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Liang, J., Li, Y., Daniels, G., Sfanos, K., De Marzo, A., Wei, J., ... Lee, P. (2015). LEF1 targeting EMT in prostate cancer invasion is regulated by miR-34a. Molecular Cancer Research, 13(4), 681-688. https://doi.org/10.1158/1541-7786.MCR-14-0503

LEF1 targeting EMT in prostate cancer invasion is regulated by miR-34a. / Liang, Jiaqian; Li, Yirong; Daniels, Garrett; Sfanos, Karen; De Marzo, Angelo; Wei, Jianjun; Li, Xin; Chen, Wenqiang; Wang, Jinhua; Zhong, Xuelin; Melamed, Jonathan; Zhao, Jun; Lee, Peng.

In: Molecular Cancer Research, Vol. 13, No. 4, 01.04.2015, p. 681-688.

Research output: Contribution to journalArticle

Liang, J, Li, Y, Daniels, G, Sfanos, K, De Marzo, A, Wei, J, Li, X, Chen, W, Wang, J, Zhong, X, Melamed, J, Zhao, J & Lee, P 2015, 'LEF1 targeting EMT in prostate cancer invasion is regulated by miR-34a', Molecular Cancer Research, vol. 13, no. 4, pp. 681-688. https://doi.org/10.1158/1541-7786.MCR-14-0503
Liang, Jiaqian ; Li, Yirong ; Daniels, Garrett ; Sfanos, Karen ; De Marzo, Angelo ; Wei, Jianjun ; Li, Xin ; Chen, Wenqiang ; Wang, Jinhua ; Zhong, Xuelin ; Melamed, Jonathan ; Zhao, Jun ; Lee, Peng. / LEF1 targeting EMT in prostate cancer invasion is regulated by miR-34a. In: Molecular Cancer Research. 2015 ; Vol. 13, No. 4. pp. 681-688.
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