[Show abstract][Hide abstract] ABSTRACT: Cellular senescence occurs as a response to extracellular and intracellular stresses and contributes to aging and age-related pathologies. Emerging evidence suggests that cellular senescence also acts as a potent tumor suppression mechanism that prevents the oncogenic transformation of primary human cells. Recent reports have indicated that miRNAsact as key modulators of cellular senescence by targeting critical regulators of the senescence pathways. We previously reported that miR-127 is up-regulated in senescent fibroblasts. In this report, we identified miR-127 as a novel regulator of cellular senescence that directly targets BCL6. We further showed that miR-127 is down-regulated in breast cancer tissuesand that this down-regulation is associated with up-regulation of BCL6. Over-expression of miR-127 or depletion of BCL6 inhibits breast cancer cell proliferation. Our data suggest that miR-127 may function as a tumor suppressor that modulates the oncogene BCL6.
PLoS ONE 11/2013; 8(11):e80266. DOI:10.1371/journal.pone.0080266 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: miRNAs are a class of non-coding RNAs that play fundamental roles through the post-transcriptional regulation of target mRNAs. miRNAs have been shown to regulate a broad spectrum of biological activities, including development, differentiation, cell death, and oncogenesis. However, little is known about their contribution to cellular senescence. The authors analyzed the expression of 576 miRNAs in proliferating and senescent normal human fibroblasts by microarray, and identified 12 miRNAs that were differentially expressed in proliferating and senescent fibroblasts. Interestingly, all six miRNAs that were down-regulated in senescent cells had been previously reported to be aberrantly expressed in tumor cells. It was further showed that inhibition of miR-17-5p and miR-20a by 2'-O-methyl antisense oligoribonucleotides resulted in the induction of senescent phenotypes in WI-38 cells.