MicroRNAs (
miRNAs) have been implicated in complex vertebrate developmental and pathological systems as a versatile class of molecules involved in the regulation of various biological processes and molecular pathways. To elucidate the role of
miRNAs in human somatic cells, an understanding of the molecular framework regulated by individual
miRNA is essential. In this study, we examined the effect of
hsa-miR-601 on gene expression changes in human
lung cancer cells A549. To achieve this,
DNA microarray and global pathway analyses were performed on
hsa-miR-601 introduced cells for two successive days. Gene ontology analysis revealed that the effect of
hsa-miR-601 over-represented the negative regulation of translation/translational initiation, whereas GenMAPP analysis revealed that several characteristic pathways were changed in
hsa-miR-601 introduced A549 cells compared to control short
RNA introduced cells. Among them, up-regulation of actin cytoskeleton and down-regulation of Fas-induced apoptosis pathway occurred on two successive days after
hsa-miR-601 introduction. Using a
luciferase reporter assay, we also showed that
hsa-miR-601 specifically repressed
nuclear factor-kappaB (
NF-kappaB)
transcription factor-dependent reporter expression, a key component of the immune-
oncogenesis pathway. These findings suggest that
hsa-miR-601 could affect a variety of signaling pathways accompanying orchestrated gene expression changes. Our results argue that individual
miRNAs affect complex regulation of cellular signaling pathways.