title: MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence.
abstract: MicroRNAs (miRNAs) are short non-coding RNAs that regulate diverse biological processes by controlling the pattern of expressed proteins. In mammalian cells, miRNAs partially complement their target sequences leading to mRNA degradation and/or decreased mRNA translation. Here, we have analyzed transcriptome-wide changes in miRNAs in senescent relative to early-passage WI-38 human diploid fibroblasts (HDFs). Among the miRNAs downregulated with senescence were members of the let-7 family, while upregulated miRNAs included miR-1204, miR-663 and miR-519. miR-519 was recently found to reduce tumor growth at least in part by lowering the abundance of the RNA-binding protein HuR. Overexpression of miR-519a in either WI-38 or human cervical carcinoma HeLa cells triggered senescence, as measured by monitoring beta-galactosidase activity and other senescence markers. These data suggest that miR-519 can suppress tumor growth by triggering senescence and that miR-519 elicits these actions by repressing HuR expression.
authors.affiliation: Laboratory of Cellular and Molecular Biology, NIA-IRP, NIH, Baltimore, MD 21224, USA.
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Marasa
authors.forename: Subramanya
authors.initials: S
authors.lastname: Srikantan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.forename: Mihee M
authors.initials: MM
authors.lastname: Kim
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D004171:Diploidy; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C546194:MIRN519 microRNA, human; D035683:MicroRNAs