Journal
CANCER GENE THERAPY
Volume 23, Issue 4, Pages 83-89Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2016.3
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Funding
- National Natural Science Foundation of China [81272418]
- National Science Foundation for Young Scientists of China [81502227, 81402506]
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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)alpha-positive breast tumor. Further, we found that only let-7c was inversely correlated with ER alpha 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 ER alpha-positive breast cancer. Let-7c decreased ER alpha expression through directly binding to the 3'UTR (untranslated region), and let-7c inhibited the estrogen-induced activation of Wnt signaling. Depletion of ER alpha abolished let-7c functions in stem cell signatures, which further confirmed that let-7c inhibited estrogen-induced Wnt activity through decreasing ER alpha expression. Taken together, our findings identified a biochemical and functional link between let-7c with ER alpha/Wnt signaling in breast cancer stem cells.
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