title: The influence of miR-34a expression on stemness and cytotoxic susceptibility of breast cancer stem cells.
abstract: In this study, we investigate the effect of miR-34a expression and biological characteristics of breast cancer stem cells (BCSCs). The mammospheres were formed from murine breast cancer cell line 4T1 and regarded as murine BCSCs. Identification of stemness molecules and cloning experiments validate the biological characteristics of BCSCs we have established. We showed that miR-34a, as a tumor suppressor, could separately reduce the stemness of BCSCs and activate the cytotoxic susceptibility of BCSCs to natural killer (NK) cells in vitro via down regulating the expression of Notch1 signaling molecules. Moreover, miR-34a could completely restrain established mice breast tumor xenografts in vivo in the NOD/SCID mice that have functional NK cells at a normal level, whereas it was less effective in NOD/SCID/ CD122/IL-2Rβ mice that do not have functional NK cells. We conclude that miR-34a is a crucial, dual tumor suppressor and BCSCs-targeting immunotherapeutic agent and has shown efficacy in the treatment of murine breast cancer. The results also suggest that impaired NK cells could contribute to the resistance to therapies.
authors.affiliation: a Medical School of Nankai University , Tianjin , China.
authors.forename: Hongyao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a Medical School of Nankai University , Tianjin , China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: a Medical School of Nankai University , Tianjin , China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a Medical School of Nankai University , Tianjin , China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Jin
authors.affiliation: a Medical School of Nankai University , Tianjin , China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Shan
authors.affiliation: a Medical School of Nankai University , Tianjin , China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Qin
authors.affiliation: a Medical School of Nankai University , Tianjin , China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs
keywords: Cytotoxic susceptibility; Notch1; ligand; miR-34a