title: miR-520h is crucial for DAPK2 regulation and breast cancer progression.
abstract: MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3'untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: C-M
authors.initials: CM
authors.lastname: Su
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: M-Y
authors.initials: MY
authors.lastname: Wang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Hong
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: H-A
authors.initials: HA
authors.lastname: Chen
authors.affiliation: Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Su
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: M-T
authors.initials: MT
authors.lastname: Huang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Chang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: S-S
authors.initials: SS
authors.lastname: Jiang
authors.affiliation: Program for Translational Medicine College of Medical Science and Technology Taipei Medical University, Taipei, Taiwan.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Sung
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Chang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: L-T
authors.initials: LT
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.|Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: P-S
authors.initials: PS
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: J-L
authors.initials: JL
authors.lastname: Su
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D064550:Death-Associated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C579104:DAPK2 protein, human; D064550:Death-Associated Protein Kinases; D017239:Paclitaxel