The culture-induced senescence of mouse embryo fibroblasts (MEF) correlates with reduction of cell proliferation. In this work we found that the accumulation of cells with 4C
DNA content and the transcriptional change of several
microRNAs (
miRNAs or miRs) are relevant events in culture senescence. By comparing the
miRNA expression profiles of physiologically senescent MEF and that of senescent MEF induced by the downregulation of
leukemia-related factor, we identified miR-290 as a common upregulated
miRNA. When miR-290 was transfected in presenescent MEF, SA-beta-gal(+) cells and p16, two markers of culture senescence, increased compared with control, indicating that miR-290 is causally involved in senescence. Interestingly,
nocodazole (NCZ), which induces G2/M block, increased the percentage of senescent cells as well as the expression of miR-290 and of the
tumor suppressor p16, thus mimicking culture senescence. As miR-290 was overexpressed in NCZ-treated cells and it was able to induce senescence in proliferating MEF, we investigated whether miR-290 and NCZ could share common mechanisms of culture senescence. Whereas the induction of SA-beta-gal(+) by miR-290 was not strengthened by coupling its transfection with NCZ treatment, the transfection of the
antagomir 290 (d-290) plus NCZ treatment, while blocking cells at G2/M, suppressed SA-beta-gal(+) and p16 induction. On the basis of these findings we conclude that miR-290 might act as a physiological effector of NCZ induced as well as culture senescence via p16 regulation expanding the role of this
miRNA from embryonic stem to differentiated cells.