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NF-κB subunit RELA suppression of mucosa-associated lymphoid tissue lymphoma translocation protein 1 expression in

Takaomi Nozawa1, Nozomi Mihara-Tomiyama1, Tadashige Chiba1

  • 1Department of Biochemistry, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.

Biochemical and Biophysical Research Communications
|January 22, 2021
PubMed

Insights

Nuclear factor-kappaB (NF-κB) subunit RELA suppresses mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) expression in oral carcinoma. This suppression may drive oral cancer progression, highlighting a new therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Loss of MALT1 expression correlates with aggressive oral carcinoma.
  • Understanding MALT1 down-regulation mechanisms is crucial for oral cancer progression pathways.
  • Transcriptional regulation of MALT1 gene down-regulation is currently unknown.

Purpose of the Study:

  • To investigate the transcriptional regulation of MALT1 gene down-regulation in oral carcinoma.
  • To identify regulatory elements and transcription factors involved in MALT1 suppression.

Main Methods:

  • Reporter assays to identify silencer regions in the MALT1 gene.
  • Chromatin immunoprecipitation (ChIP) to confirm transcription factor binding.
  • Site-directed mutagenesis and deletion analysis of the MALT1 gene.
  • Short interfering RNA (siRNA) knockdown of RELA.

Main Results:

  • A silencer region between +402 and +501 of the MALT1 gene was identified.
  • This region contains a binding site for nuclear factor-kappaB (NF-κB) subunit RELA.
  • RELA binding was confirmed by ChIP and reduced by site mutations.
  • RELA knockdown and MALT1 binding site mutations increased MALT1 expression.

Conclusions:

  • RELA binds to a specific site on the MALT1 gene, suppressing its expression.
  • This RELA-mediated suppression of MALT1 may contribute to oral carcinoma progression.
  • Targeting the RELA-MALT1 interaction could offer a therapeutic strategy for oral cancer.
Keywords:
Mucosa-associated lymphoid tissue lymphoma translocation protein 1NF-κBOral carcinomaRepressor proteins

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