title: Upregulation of miR-760 and miR-186 is associated with replicative senescence in human lung fibroblast cells.
abstract: We have previously shown that microRNAs (miRNAs) miR-760, miR-186, miR-337-3p, and miR-216b stimulate premature senescence through protein kinase CK2 (CK2) down-regulation in human colon cancer cells. Here, we examined whether these four miRNAs are involved in the replicative senescence of human lung fibroblast IMR-90 cells. miR-760 and miR-186 were significantly upregulated in replicatively senescent IMR-90 cells, and their joint action with both miR-337-3p and miR-216b was necessary for efficient downregulation of the α subunit of CK2 (CK2α) in IMR-90 cells. A mutation in any of the four miRNA-binding sequences within the CK2α 3'-untranslated region (UTR) indicated that all four miRNAs should simultaneously bind to the target sites for CK2α downregulation. The four miRNAs increased senescence-associated β-galactosidase (SA-β-gal) staining, p53 and p21(Cip1/WAF1) expression, and reactive oxygen species (ROS) production in proliferating IMR-90 cells. CK2α over-expression almost abolished this event. Taken together, the present results suggest that the upregulation of miR-760 and miR-186 is associated with replicative senescence in human lung fibroblast cells, and their cooperative action with miR-337-3p and miR-216b may induce replicative senescence through CK2α downregulation-dependent ROS generation.
authors.affiliation: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Lee
authors.affiliation: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C533096:MIRN186 microRNA, human; C575482:MIRN216 microRNA, human; C579293:MIRN760 microRNA, human; D035683:MicroRNAs; C544075:Mirn337 microRNA, human; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II
keywords: human lung fibroblast; miRNA; protein kinase CK2; reactive oxygen species; replicative senescence