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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-5
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1945-7197
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1421-30
pubmed:meshHeading
pubmed-meshheading:20061417-Analysis of Variance, pubmed-meshheading:20061417-Animals, pubmed-meshheading:20061417-Apoptosis, pubmed-meshheading:20061417-Blotting, Western, pubmed-meshheading:20061417-Carcinoma, pubmed-meshheading:20061417-Cell Line, Tumor, pubmed-meshheading:20061417-Cell Proliferation, pubmed-meshheading:20061417-Cells, Cultured, pubmed-meshheading:20061417-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20061417-Humans, pubmed-meshheading:20061417-Immunohistochemistry, pubmed-meshheading:20061417-Mice, pubmed-meshheading:20061417-MicroRNAs, pubmed-meshheading:20061417-Microarray Analysis, pubmed-meshheading:20061417-NF-kappa B, pubmed-meshheading:20061417-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20061417-Thyroid Neoplasms, pubmed-meshheading:20061417-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Nuclear factor-{kappa}B contributes to anaplastic thyroid carcinomas through up-regulation of miR-146a.
pubmed:affiliation
Dipartimento di Biologia e Patologia Cellulare e Molecolare, "Federico II" University of Naples, Via S. Pansini 5, 80131 Naples, Italy.
pubmed:publicationType
Journal Article