title: miR-1 induces growth arrest and apoptosis in malignant mesothelioma.
abstract: BACKGROUND
  We investigated microRNA expression profiles of malignant pleural mesothelioma (MPM) specimens to identify novel microRNA that are potentially involved in the oncogenic transformation of human pleural cells.
  
  
  METHODS
  microRNA microarray transcriptional profiling studies of 25 MPM primary tumors were performed. We used normal pleural tissue from an unmatched patient cohort as normal comparators. To confirm microarray data, we used real-time quantitative polymerase chain reaction. Representative cell lines H513 and H2052 were used in functional analyses of miR-1.
  
  
  RESULTS
  In addition to several novel MPM-associated microRNAs, we observed that the expression level of miR-1 was significantly lower in tumors as compared with normal pleural specimens. Subsequently, pre-miR of miR-1 was introduced into MPM cell lines to overexpress this microRNA. Phenotypic changes of these altered cells were assayed. The cellular proliferation rate was significantly inhibited after overexpression of miR-1. Early and late apoptosis was increased markedly in miR-1-transfected cell lines. Taken together, these data suggested that overexpression of miR-1 induced apoptosis in these MPM cell lines, acting as a tumor suppressor. We confirmed our observations by assessing in the transduced MPM cells cell cycle-related, proapoptotic, and antiapoptotic genes, which all showed coordinated, significant changes characteristic of the apoptotic phenotype.
  
  
  CONCLUSIONS
  Further investigation and validation of our microRNA database of MPM may elucidate previously unrecognized molecular pathways and/or mechanisms by identifying novel microRNAs that are involved in malignant transformation. Our study has now found miR-1 to be one of these MPM-associated microRNAs, with potential pathogenic and therapeutic significance.
authors.affiliation: Division of Thoracic Surgery, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiothoracic Surgery, Department of Anesthesia, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Division of Thoracic Surgery, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Merritt
authors.affiliation: Division of Thoracic Surgery, Department of Medicine, Stanford University School of Medicine, Stanford, CA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Shrager
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
authors.affiliation: Division of Hematology, Oncology, and Transplant, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.affiliation: Division of Thoracic Surgery, Department of Medicine, Stanford University School of Medicine, Stanford, CA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA. Electronic address: cdhoang@stanford.edu.
authors.forename: Chuong D
authors.initials: CD
authors.lastname: Hoang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000086002:Mesothelioma, Malignant; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm