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

الملخص EN

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 (P<0.05).

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 (P<0.05).

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.