title: Let-7: a regulator of the ERα signaling pathway in human breast tumors and breast cancer stem cells.
abstract: The oncogenic role of estrogen receptor (ER)α and its correlation with let-7 microRNAs (miRNAs) have been studied and confirmed in breast tumors; however, this correlation has not been investigated in breast cancer stem cells (BCSCs). In the present study, we detected the expression of let-7 and ERα in ER-positive breast tumor tissues. Furthermore, we used a FACSAria cell sorter to separate side population (SP) cells from the MCF-7 and T47-D cell lines by Hoechst 33342 staining. The expression of let-7 miRNAs, ERα and its downstream genes in SP and non-SP (NSP) cells were analyzed. In additional experiments, we transfected a plasmid expressing let-7a into SP cells isolated from the MCF-7 and T47-D cell lines in order to observe changes in the expression of downstream genes (cyclin D1 and pS2). The correlation among let-7, ERα and ERα downstream genes suggested that let-7 acts as a tumor suppressor by inhibiting ERα-mediated cellular malignant growth in ER-positive breast cancer stem cells. The suppression of ERα by the upregulation of let-7 expression may be a promising strategy for the inhibition of the ER signaling pathway and for the elimination of cancer stem cells, thus aiding in the treatment of breast cancer.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Sida
authors.initials: S
authors.lastname: Qin
authors.forename: Chong
authors.initials: C
authors.lastname: Fan
authors.forename: Chongwen
authors.initials: C
authors.lastname: Xu
authors.forename: Ning
authors.initials: N
authors.lastname: Du
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D058985:Side-Population Cells / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D047628:Estrogen Receptor alpha; D035683:MicroRNAs; C508861:PSEN2 protein, human; D053766:Presenilin-2; C487931:mirnlet7 microRNA, human; D019938:Cyclin D1