title: 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.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Otorhinolaryngology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: C
authors.initials: C
authors.lastname: Xu
authors.affiliation: Breast Cancer Program and Interdisciplinary Translational Research Team, Georgia Regents University Cancer Center, Augusta, Georgia, USA.|Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: S-C
authors.initials: SC
authors.lastname: Tang
authors.affiliation: Department of Vascular and Endovascular Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: N
authors.initials: N
authors.lastname: Du
authors.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: S
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Tianjin Cancer Institute and Hospital Affiliated to Tianjin Medical University, Tianjin, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Ren
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000187:drug effects; D016000:Cluster Analysis; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human