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

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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

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Neoplastic Stem Cells
Estrogen Receptors
Estrogens
Breast Neoplasms
3' Untranslated Regions
MicroRNAs
Carcinogenesis
Stem Cells
Research
Neoplasms

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells. / Sun, X.; Xu, C.; Tang, Shou-Ching; Wang, J.; Wang, H.; Wang, P.; Du, N.; Qin, S.; Li, G.; Xu, S.; Tao, Z.; Liu, Dapeng; Ren, H.

In: Cancer Gene Therapy, Vol. 23, No. 4, 01.04.2016, p. 83-89.

Research output: Contribution to journalArticle

Sun, X, Xu, C, Tang, S-C, Wang, J, Wang, H, Wang, P, Du, N, Qin, S, Li, G, Xu, S, Tao, Z, Liu, D & Ren, H 2016, 'Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells', Cancer Gene Therapy, vol. 23, no. 4, pp. 83-89. https://doi.org/10.1038/cgt.2016.3
Sun, X. ; Xu, C. ; Tang, Shou-Ching ; Wang, J. ; Wang, H. ; Wang, P. ; Du, N. ; Qin, S. ; Li, G. ; Xu, S. ; Tao, Z. ; Liu, Dapeng ; Ren, H. / Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells. In: Cancer Gene Therapy. 2016 ; Vol. 23, No. 4. pp. 83-89.
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