Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells

X. Sun, C. Xu, Shou-Ching Tang, J. Wang, H. Wang, P. Wang, N. Du, S. Qin, G. Li, S. Xu, Z. Tao, Dapeng Liu, H. Ren

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Let-7 miRNAs are involved in carcinogenesis and tumor progression through their roles in maintaining differentiation and normal development. However, there is little research focusing on the effects of let-7 on Wnt-activated self-renewal of breast cancer stem cells. By analyzing the expression levels of let-7 family members in clinical tissues, we found that higher expression levels of let-7b and let-7c were correlated with better clinical prognosis of patients with estrogen receptor (ER)α-positive breast tumor. Further, we found that only let-7c was inversely correlated with ERα expression, and there is corelationship between let-7c and Wnt signaling in clinical tissues. Aldehyde dehydrogenase (ALDH)1 sorting and mammosphere formation assays showed that let-7c inhibited the self-renewal of stem cells in ERα-positive breast cancer. Let-7c decreased ERα expression through directly binding to the 3'UTR (untranslated region), and let-7c inhibited the estrogen-induced activation of Wnt signaling. Depletion of ERα abolished let-7c functions in stem cell signatures, which further confirmed that let-7c inhibited estrogen-induced Wnt activity through decreasing ERα expression. Taken together, our findings identified a biochemical and functional link between let-7c with ERα/Wnt signaling in breast cancer stem cells.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalCancer Gene Therapy
Volume23
Issue number4
DOIs
StatePublished - Apr 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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