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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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