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.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Sun X,Xu C,Tang SC,Wang J,Wang H,Wang P,Du N,Qin S,Li G,Xu S,Tao Z,Liu D,Ren H

doi

10.1038/cgt.2016.3

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

83-9

issue

4

eissn

0929-1903

issn

1476-5500

pii

cgt20163

journal_volume

23

pub_type

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