title: MicroRNA-101 inhibits cell proliferation and induces apoptosis by targeting EYA1 in breast cancer.
abstract: MicroRNAs (miRNAs or miRs) regulate gene expression by negatively modulating the stability or translational efficiency of their target genes by targeting the 3'-untranslated region (3'-UTR). Aberrant miRNA expression has been reported in various types of cancer; miRNAs can function as either oncogenes or tumor suppressor genes in cancer. In this study, we examined the expression level of miR‑101 in breast cancer tissues and cell lines by RT-qPCR, and found that miR‑101 expression was downregulated in breast cancer tissues and cell lines; indeed, in 6 of the 28 tissue samples, miR‑101 could not be detected. Furthermore, miR‑101, when transfected into SKBR3 cells, inhibited cell proliferation and promoted apoptosis, while miR‑101 inhibitor had the opposite effect. A dual-luciferase reporter assay revealed that miR‑101 targeted the 3'-UTR of eyes absent homolog 1 (Drosophila) (EYA1). Western blot analysis demonstrated a significantly decreased protein level of EYA1 in the SKBR3 cells transfected with miR‑101 mimic, whereas transfection with miR‑101 inhibitor led to an increased level of EYA1. Moreover, an increased expression of EYA1 was also found in breast cancer tissues and cell lines. The silencing of EYA1 using siRNA targeting EYA1 (EYA1‑siRNA) significantly inhibited SKBR3 cell proliferation and promoted apoptosis, and also suppressed the increased proliferation induced by transfection with miR‑101 inhibitor. The protein expression levels of Notch signaling components (jagged1, Hes1 and Hey1) were significantly decreased by transfection with miR‑101 mimic and EYA1-siRNA, and were increased by transfection with miR‑101 inhibitor. Furthermore, the elevated protein expression levels of jagged1, Hes1 and Hey1 induced by transfection with miR‑101 inhibitor in the SKBR3 cells were significantly decreased by transfection with EYA1-siRNA. Taken together, these results suggest that miR‑101 is down-regulated in breast cancer, and can inhibit cell proliferation and promote apoptosis by targeting EYA1 through the Notch signaling pathway.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Liu
authors.forename: Xijing
authors.initials: X
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000072100:Jagged-1 Protein / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D035683:MicroRNAs; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D017027:Protein Tyrosine Phosphatases; D034741:RNA, Small Interfering; D000072056:Transcription Factor HES-1; C485631:HEY1 protein, human; C534072:MIRN101 microRNA, human; C078493:HES1 protein, human; C104381:EYA1 protein, human