Nuclear factor-{kappa}B contributes to anaplastic thyroid carcinomas through up-regulation of miR-146a.
Context: Micro-RNAs (miRNAs) have been recently involved in the modulation of several biological activities including cancer. Many human tumors show deregulated expression of miRNAs targeting oncogenes and/or tumor suppressors, thus identifying miRNAs as new molecular targets for cancer therapy. Objectives: Nuclear factor (NF)-kappaB is strongly activated in human anaplastic thyroid carcinomas (ATCs). Because the regulation of miRNA expression is under control of RNA polymerase II-dependent transcription factors, we stably inactivated NF-kappaB in the ATC-derived FRO cell line and analyzed its miRNA profile in comparison with the parental counterpart by using a miRNA chip microarray. Results: The analysis revealed that a number of miRNAs were differentially expressed in the two cell lines. Among others, the miR-146a showed a strong down-regulation that was confirmed by quantitative real time RT-PCR. The expression of miR-146a was almost undetectable in mouse embryonic fibroblasts isolated from the RelA knockout mice and was restored after reexpression of RelA, thus indicating that miR-146a transcription was controlled by NF-kappaB. The inhibition of miR-146a expression in FRO cells decreased their oncogenic potential and increased the susceptibility to chemotherapeutic drug-induced apoptosis. No difference was found in the growth rate between untransfected and miR-146a-null FRO cells. Importantly, the miR-146a resulted in overexpression of human ATC specimens compared with the normal thyroid tissue. Conclusions: Our results show that NF-kappaB contributes to anaplastic thyroid cancer up-regulating the expression of miR-146a.[1]References
- Nuclear factor-{kappa}B contributes to anaplastic thyroid carcinomas through up-regulation of miR-146a. Pacifico, F., Crescenzi, E., Mellone, S., Iannetti, A., Porrino, N., Liguoro, D., Moscato, F., Grieco, M., Formisano, S., Leonardi, A. J. Clin. Endocrinol. Metab. (2010) [Pubmed]
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