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.

Abstract

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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