title: Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma.
abstract: Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis. Downregulation of miR-26a or miR-26b was confirmed in RCC clinical specimens. Restoration of miR-26a or miR-26b in RCC cell lines (786-O and A498) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analysis and luciferase reporter assays showed that lysyl oxidase-like 2 (LOXL2) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were directly regulated by these miRNAs. Moreover, downregulating the PLOD2 gene significantly inhibited cell migration and invasion in RCC cells. Thus, our data showed that two genes promoting metastasis, LOXL2 and PLOD2, were epigenetically regulated by tumor-suppressive microRNAs, miR-26a and miR-26b, providing important insights into the molecular mechanisms of RCC metastasis.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurozumi
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsushita
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okato
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fukumoto
authors.affiliation: Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics*
chemical_list: D000594:Amino Acid Oxidoreductases; D035683:MicroRNAs; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; C528163:MIRN26 microRNA, human; C479138:PLOD2 protein, human; C119091:LOXL2 protein, human