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Suppression of KLF5 basal expression in oral carcinoma-derived cells through three intact CREB1-binding sites in the

Reiichi Katsuumi1, Tsubasa Negishi1, Kazushi Imai1

  • 1Department of Biochemistry, The Nippon Dental University School of Life Dentistry at Tokyo, Japan.

Journal of Oral Biosciences
|December 26, 2023
PubMed
Abstract

Insights

Cyclic AMP responsive element binding protein 1 (CREB1) binding to the KLF5 silencer suppresses oral cancer progression. All three CREB1-binding sites must be intact to inhibit KLF5 basal expression in oral carcinoma cells.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Krüppel-like factor (KLF)5 is overexpressed in oral cancer, inhibiting epidermal differentiation and promoting carcinoma progression.
  • The regulatory mechanisms governing KLF5 gene transcription, particularly in oral cancer, remain unclear.

Purpose of the Study:

  • To investigate the transcriptional regulation of the KLF5 gene, focusing on a specific silencer region.
  • To elucidate the role of cAMP responsive element binding protein 1 (CREB1) in KLF5 gene expression in oral carcinoma cells.

Main Methods:

  • Reporter assays were used to examine the transcriptional activity of the KLF5 425-bp silencer region and its minimal essential region (MER).
  • DNA pull-down and quantitative chromatin immunoprecipitation assays assessed CREB1 binding affinity to three putative binding sites within the 425-region.
  • Reporter assays in HSC2 oral squamous carcinoma cells involved CREB1 knockdown and overexpression to evaluate the impact of binding sites on MER activity.

Main Results:

  • The 425-region suppressed MER transcriptional activity and contained three CREB1-binding sites with equal binding affinity.
  • Deletion of CREB1-binding sites reduced CREB1 precipitation and enhanced MER activity.
  • CREB1 knockdown and overexpression modulated MER activity at intact sites, with site deletion affecting this modulation.

Conclusions:

  • CREB1 binding to the KLF5 425-bp silencer region suppresses KLF5 basal expression in oral carcinoma cells.
  • Intactness of all three CREB1-binding sites is crucial for this suppression.
  • Deletion of CREB1-binding sites relieves the suppression of KLF5 basal expression, suggesting a mechanism for KLF5 regulation in oral cancer.
Keywords:
CREB1CarcinomaGene expressionKLF5Transcription factors

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