title: Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that is refractory to treatment and carries a high mortality rate. IPF is frequently associated with lung cancer. Identification of molecular targets involved in both diseases may elucidate novel molecular mechanisms contributing to their pathology. Recent studies of microRNA (miRNA) expression signatures showed that microRNA-29a (miR-29a) was downregulated in IPF and lung cancer. The aim of this study was to investigate the functional significance of miR-29a in lung cancer cells (A549 and EBC-1) and lung fibroblasts (MRC-5) and to identify molecular targets modulated by miR-29a in these cells. We confirmed the downregulation of miR-29a in clinical specimens of IPF and lung cancer. Restoration of miR-29a suppressed cancer cell aggressiveness and fibroblast migration. A combination of gene expression data and in silico analysis showed that a total of 24 genes were putative targets of miR-29a. Among them, lysyl oxidase-like 2 (LOXL2) and serpin peptidase inhibitor clade H, member 1 (SERPINH1) were direct targets of miR-29a by luciferase reporter assays. The functions of LOXL2 and SERPINH1 contribute significantly to collagen biosynthesis. Overexpression of LOXL2 and SERPINH1 was observed in clinical specimens of lung cancer and fibrotic lesions. Downregulation of miR-29a caused overexpression of LOXL2 and SERPINH1 in lung cancer and IPF, suggesting that these genes are involved in the pathogenesis of these two diseases.
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kamikawaji
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mataki
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kumamoto
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012008:Recurrence
chemical_list: D050958:HSP47 Heat-Shock Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C494660:SERPINH1 protein, human; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human