MicroRNAs (
miRNAs) are
small noncoding RNA molecules that interact with target mRNAs at specific sites to induce cleavage of the
mRNA or inhibit translation. Such
miRNAs play a vital role in gene expression and in several other biological processes, including cell death. We have studied the mechanisms regulating cell death (
necrosis in original F28-7 cells and apoptosis in their variant F28-7-A cells) in the mouse mammary tumor cell line FM3A using the
anticancer agent floxuridine (
FUdR). We previously reported that inhibition of
heat-shock protein 90 by the specific inhibitor
geldanamycin (GA) in F28-7 cells causes a shift from
necrosis to apoptosis. In this study, we investigated the intracellular
miRNA expression profiles of
FUdR-treated F28-7 cells (necrotic condition), GA plus
FUdR-treated F28-7 cells (apoptotic condition), and
FUdR-treated F28-7-A cells (apoptotic condition) through
miRNA microarray analysis. In addition, we knocked down Dicer, a key molecule for the expression of mature
miRNAs, in F28-7 cells to examine whether it modulates
FUdR-induced cell death. Our analysis revealed that the
miRNA expression patterns differ significantly between these cell death conditions. Furthermore, we identified
miRNA candidates that regulate cell death. Knockdown of Dicer in
FUdR-treated
necrosis-fated cells caused a partial shift from
necrosis to apoptosis. These findings suggest that modulation of
miRNA expression patterns influences the decision of cell death fate toward
necrosis or apoptosis. Our findings may serve as a basis for further study of the functions of
miRNAs in cell death mechanisms.