Inhibition of cell viability by human IFN-β is mediated by microRNA-431.

MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression by cleaving or hindering the translation of target mRNAs. We used microarray-based comparative transcriptome analysis to identify changes in miRNA expression and function between a human cell line, RSa, which is highly sensitive to HuIFN-β-mediated inhibition of cell viability, and its variant, the F-IFr cell line, which is relatively resistant to the cytokine. miR-431 expression was significantly higher in RSa cells compared with F-IFr cells. The addition of HuIFN-β to RSa cultures reduced cell viability, down-regulated expression of IGF1R and IRS2 (putative miR-431 target genes), and inhibited the PI3K-Akt and MAPK pathways. The survival of F-IFr cells was not reduced by HuIFN-β, but transient transfection with miR-431 precursors significantly decreased viability and concomitantly down-regulated IGF1R and IRS2 expression. In addition, the MAPK pathway, but not the PI3K-Akt pathway, was suppressed in F-IFr cells. Based on these results, we propose that, in RSa cells, HuIFN-β-induced miR-431 expression may down-regulate IGF1R and IRS2 expression, and consequently inhibit cell proliferation by suppressing the MAPK pathway.