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Updated: Jun 17, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Nuclear factor-{kappa}B contributes to anaplastic thyroid carcinomas through up-regulation of miR-146a
Francesco Pacifico1, Elvira Crescenzi, Stefano Mellone
1Dipartimento di Biologia e Patologia Cellulare e Molecolare, "Federico II" University of Naples, Via S. Pansini 5, 80131 Naples, Italy.
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.
Insights
Nuclear factor-kappaB (NF-kappaB) up-regulates micro-RNA 146a (miR-146a) in anaplastic thyroid cancer. This miRNA inhibition reduces cancer
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Micro-RNAs (miRNAs) play a role in cancer by regulating oncogenes and tumor suppressors.
- miRNAs are emerging as potential therapeutic targets in cancer treatment.
- Anaplastic thyroid carcinomas (ATCs) exhibit significant activation of Nuclear Factor-kappaB (NF-kappaB).
Purpose of the Study:
- To investigate the role of NF-kappaB in regulating miRNA expression in anaplastic thyroid cancer.
- To analyze the miRNA profile of anaplastic thyroid carcinoma cells with inactivated NF-kappaB.
- To determine the functional impact of specific miRNA changes on cancer progression.
Main Methods:
- Stable inactivation of NF-kappaB in the ATC-derived FRO cell line.
- miRNA chip microarray analysis to compare miRNA profiles.
- Quantitative real-time RT-PCR to validate miRNA expression levels.
- RelA re-expression in knockout mouse embryonic fibroblasts to confirm NF-kappaB control.
- Assessment of oncogenic potential and chemosensitivity in modified cells.
Main Results:
- NF-kappaB inactivation led to differential expression of several miRNAs in FRO cells.
- miR-146a was significantly down-regulated upon NF-kappaB inactivation and its expression is controlled by NF-kappaB.
- Inhibition of miR-146a reduced the oncogenic potential and increased apoptosis susceptibility in FRO cells.
- miR-146a was overexpressed in human ATC specimens compared to normal thyroid tissue.
Conclusions:
- NF-kappaB activation contributes to anaplastic thyroid cancer progression.
- NF-kappaB up-regulates the expression of miR-146a in anaplastic thyroid cancer.
- miR-146a may serve as a potential therapeutic target in anaplastic thyroid cancer.
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