Expression of Senescence-Associated microRNAs and Target Genes in Cellular Aging and Modulation by Tocotrienol-Rich FractionReportar como inadecuado

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Oxidative Medicine and Cellular Longevity - Volume 2014 2014, Article ID 725929, 12 pages -

Research ArticleDepartment of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

Received 8 April 2014; Revised 2 June 2014; Accepted 2 June 2014; Published 14 July 2014

Academic Editor: Narasimham L. Parinandi

Copyright © 2014 Sharon Gwee Sian Khee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Emerging evidences highlight the implication of microRNAs as a posttranscriptional regulator in aging. Several senescence-associated microRNAs SA-miRNAs are found to be differentially expressed during cellular senescence. However, the role of dietary compounds on SA-miRNAs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction TRF on SA-miRNAs miR-20a, miR-24, miR-34a, miR-106a, and miR-449a and established target genes of miR-34a CCND1, CDK4, and SIRT1 during replicative senescence of human diploid fibroblasts HDFs. Primary cultures of HDFs at young and senescent were incubated with TRF at 0.5 mg-mL. Taqman microRNA assay showed significant upregulation of miR-24 and miR-34a and downregulation of miR-20a and miR-449a in senescent HDFs . TRF reduced miR-34a expression in senescent HDFs and increased miR-20a expression in young HDFs and increased miR-449a expression in both young and senescent HDFs. Our results also demonstrated that ectopic expression of miR-34a reduced the expression of CDK4 significantly . TRF inhibited miR-34a expression thus relieved its inhibition on CDK4 gene expression. No significant change was observed on the expression of CCND1, SIRT1, and miR-34a upstream transcriptional regulator, TP53. In conclusion tocotrienol-rich fraction prevented cellular senescence of human diploid fibroblasts via modulation of SA-miRNAs and target genes expression.

Autor: Sharon Gwee Sian Khee, Yasmin Anum Mohd Yusof, and Suzana Makpol



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