p16(INK4a) Translation Suppressed by miR-24

BACKGROUND: Expression of the tumor suppressor p16(INK4a) increases during aging and replicative senescence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with rep...

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Detalles Bibliográficos
Autores principales: Lal, Ashish, Kim, Hyeon Ho, Abdelmohsen, Kotb, Kuwano, Yuki, Pullmann, Rudolf, Srikantan, Subramanya, Subrahmanyam, Ramesh, Martindale, Jennifer L., Yang, Xiaoling, Ahmed, Fariyal, Navarro, Francisco, Dykxhoorn, Derek, Lieberman, Judy, Gorospe, Myriam
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2274865/
https://www.ncbi.nlm.nih.gov/pubmed/18365017
http://dx.doi.org/10.1371/journal.pone.0001864
Descripción
Sumario:BACKGROUND: Expression of the tumor suppressor p16(INK4a) increases during aging and replicative senescence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of miR-24, a microRNA that was predicted to associate with the p16 mRNA coding and 3′-untranslated regions. Ectopic miR-24 overexpression reduced p16 protein but not p16 mRNA levels. Conversely, introduction of antisense (AS)-miR-24 blocked miR-24 expression and markedly enhanced p16 protein levels, p16 translation, and the production of EGFP-p16 reporter bearing the miR-24 target recognition sites. CONCLUSIONS/SIGNIFICANCE: Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation.

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