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

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.

• Authors: X Sun, C Xu, S-C Tang, J Wang, H Wang, P Wang, N Du, S Qin, G Li, S Xu, Z Tao, Dapeng Liu, H Ren
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 23 Issue 4 Pg. 83-9 (Apr 2016) ISSN: 1476-5500 [Electronic] England
• PMID: 26987290 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• ESR1 protein, human
• Estrogen Receptor alpha
• Estrogens
• MicroRNAs
• mirnlet7 microRNA, human

Topics

• 3' Untranslated Regions
• Binding Sites
• Breast Neoplasms (genetics, metabolism, mortality)
• Cell Line, Tumor
• Cell Self Renewal (drug effects)
• Cluster Analysis
• Estrogen Receptor alpha (genetics, metabolism)
• Estrogens (metabolism, pharmacology)
• Female
• Gene Expression
• Gene Expression Profiling
• Humans
• MicroRNAs (genetics)
• Models, Biological
• Neoplastic Stem Cells (cytology, metabolism)
• Prognosis
• Signal Transduction (drug effects)
• Wnt Signaling Pathway (drug effects)