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Research Paper|Volume 2, Issue 6|pp 333—343

MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence

Bernard S. Marasa1,2, Subramanya Srikantan1, Jennifer L. Martindale1, Mihee M. Kim1, Eun Kyung Lee1, Myriam Gorospe1, Kotb Abdelmohsen1
  • 1Laboratory of Cellular and Molecular Biology, NIA-IRP, NIH, Baltimore, MD 21224, USA
  • 2Department of Biology, The Catholic University of America, Washington, DC 20064, USA
Received: May 21, 2010Accepted: June 17, 2010Published: June 19, 2010
https://doi.org/10.18632/aging.100159

Copyright: © 2010 Marasa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 β-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.