Antitumor activity induced by regulatory RNA: possible role of RNA-dependent protein kinase and nuclear factor-kappaB

Regulatory RNAs are noncoding RNAs that can regulate gene expression. Our previous results showed that regulatory RNAs can induce the production of interleukin-1, interleukin-2, interleukin-8, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and Fas ligand (FasL). These cytokines and FasL are involved in host defense mechanisms against tumors. B16-F10 melanoma cells are highly metastatic to the lungs and we showed that lymphocytes treated with the regulatory B16-RNA reduce significantly the number of metastatic nodules. We also found that B16-RNA activates RNA-dependent protein kinase (PKR) and the active B16-RNA fraction is polyadenylated with a sedimentation coefficient of 18S. Our findings suggest that the antitumor activity of B16-RNA is mediated by PKR through activation of the transcription factor NF-kappaB. Thus, B16-RNA may act as a regulatory RNA and may regulate gene expression at transcriptional level. This study provides the rationale for the use of B16-RNA as an immunomodulator in melanoma.