title: miR-155 downregulates ErbB2 and suppresses ErbB2-induced malignant transformation of breast epithelial cells.
abstract: ErbB2 is a vital breast cancer gene and its overexpression has a decisive role in breast tumor initiation and malignant progression. However, the molecular mechanisms that underlie ErbB2 dysregulation in breast cancer cells remain incompletely understood. In this study, we found that ErbB2 expression is inversely correlated with the level of miR-155, a well-documented oncogenic miRNA, in ErbB2-positive breast tumors. We further determined that miR-155 potently suppresses ErbB2 in breast cancer cells. Mechanistically, miR-155 acts to downregulate ErbB2 via two distinct mechanisms. First, miR-155 represses ErbB2 transcription by targeting HDAC2, a transcriptional activator of ErbB2. Second, miR-155 directly targets ErbB2 via a regulatory element in its coding region. Intriguingly, miR-155 is upregulated by trastuzumab and in turn leads to a reduction of ErbB2 expression in trastuzumab-treated ErbB2-positive breast cancer cells. Functional studies showed that miR-155 inhibits ErbB2-induced malignant transformation of human breast epithelial cells. Thus, our findings reveal an intriguing miR-155-ErbB2 context in regulating the malignant transformation of breast epithelial cells, and thereby indicate a novel mode of action for miR-155 in ErbB2-positive breast cancer.
authors.affiliation: Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China.|Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: X-H
authors.initials: XH
authors.lastname: He
authors.affiliation: Department of General Surgery, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China.|Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China.|Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of General Surgery, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
authors.forename: H-W
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China.|Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
authors.forename: M-F
authors.initials: MF
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D064593:Heterografts; D056464:Histone Deacetylase 2 / Q000235:genetics; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics; D000068878:Trastuzumab / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D035683:MicroRNAs; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D012097:Repressor Proteins; D000068878:Trastuzumab; C524942:MIRN155 microRNA, human; C486544:HDAC9 protein, human