title: MicroRNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway.
abstract: MicroRNAs play pivotal roles in cancer stem cell regulation. Previous studies have shown that microRNA-34a (miR-34a) is downregulated in human breast cancer. However, it is unknown whether and how miR-34a regulates breast cancer stem cells. Notch signaling is one of the most important pathways in stem cell maintenance and function. In this study, we verified that miR-34a directly and functionally targeted Notch1 in MCF-7 cells. We reported that miR-34a negatively regulated cell proliferation, migration, and invasion and breast cancer stem cell propagation by downregulating Notch1. The expression of miR-34a was negatively correlated with tumor stages, metastasis, and Notch1 expression in breast cancer tissues. Furthermore, overexpression of miR-34a increased chemosensitivity of breast cancer cells to paclitaxel (PTX) by downregulating the Notch1 pathway. Mammosphere formation and expression of the stemness factor ALDH1 were also reduced in the cells treated with miR-34a and PTX compared to those treated with PTX alone. Taken together, our results indicate that miR-34a inhibited breast cancer stemness and increased the chemosensitivity to PTX partially by downregulating the Notch1 pathway, suggesting that miR-34a/Notch1 play an important role in regulating breast cancer stem cells. Thus miR-34a is a potential target for prevention and therapy of breast cancer.
authors.affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China.|Department of Pathophysiology, Medical College of Dalian University, Dalian, China.
authors.forename: Le
authors.initials: L
authors.lastname: Kang
authors.affiliation: Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pathophysiology, Medical College of Dalian University, Dalian, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
authors.forename: Jiazhi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China.|Department of Pharmacology, School of Basic Medical Sciences, Peking University and State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
authors.affiliation: Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000502:physiology*; D017239:Paclitaxel / Q000627:therapeutic use; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D051881:Receptor, Notch1; D017239:Paclitaxel
keywords: Breast cancer stem cell; Notch1; drug resistance; miR-34a; paclitaxel