MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence.
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.
Marasa
Bernard S
BS
Laboratory of Cellular and Molecular Biology, NIA-IRP, NIH, Baltimore, MD 21224, USA.
Srikantan
Subramanya
S
Martindale
Jennifer L
JL
Kim
Mihee M
MM
Lee
Eun Kyung
EK
Gorospe
Myriam
M
Abdelmohsen
Kotb
K
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
C546194:MIRN519 microRNA, human; D035683:MicroRNAs