1. Academic Validation
  2. Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer

Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer

  • Clin Epigenetics. 2022 Nov 12;14(1):147. doi: 10.1186/s13148-022-01370-z.
Kanto Shozu # 1 2 Syuzo Kaneko # 3 4 Norio Shinkai # 1 5 6 Ai Dozen 1 Hirofumi Kosuge 7 Makoto Nakakido 7 Hidenori Machino 1 5 Ken Takasawa 1 5 Ken Asada 1 5 Masaaki Komatsu 1 5 Kouhei Tsumoto 7 Shin-Ichi Ohnuma 8 9 Ryuji Hamamoto 10 11
Affiliations

Affiliations

  • 1 Division of Medical AI Research and Development, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
  • 2 Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan.
  • 3 Division of Medical AI Research and Development, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan. [email protected].
  • 4 RIKEN Center for Advanced Intelligence Project, Cancer Translational Research Team, Tokyo, Japan. [email protected].
  • 5 RIKEN Center for Advanced Intelligence Project, Cancer Translational Research Team, Tokyo, Japan.
  • 6 Department of NCC Cancer Science, Biomedical Science and Engineering Track, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • 7 School of Engineering, The University of Tokyo, Tokyo, Japan.
  • 8 UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
  • 9 Department of Oncology, The Hutchison/MRC Research Center, University of Cambridge, Hills Road, Cambridge, CB2 2XZ, UK.
  • 10 Division of Medical AI Research and Development, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan. [email protected].
  • 11 RIKEN Center for Advanced Intelligence Project, Cancer Translational Research Team, Tokyo, Japan. [email protected].
  • # Contributed equally.
Abstract

Background: Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-stage epithelial cancers and plays a role in regulating the epithelial-mesenchymal transition by altering cell-cell adhesion. Although PRELP is an important factor in the development and progression of bladder Cancer, the mechanism of PRELP gene repression remains unclear.

Results: Here, we show that repression of PRELP mRNA expression in bladder Cancer cells is alleviated by HDAC inhibitors (HDACi) through histone acetylation. Using ChIP-qPCR analysis, we found that acetylation of lysine residue 5 of histone H2B in the PRELP gene promoter region is a marker for the de-repression of PRELP expression.

Conclusions: These results suggest a mechanism through which HDACi may partially regulate the function of PRELP to suppress the development and progression of bladder Cancer. Some HDACi are already in clinical use, and the findings of this study provide a mechanistic basis for further investigation of HDACi-based therapeutic strategies.

Keywords

Bladder cancer; Extracellular matrix proteins; Gene expression; H2BK5ac; HDACi; PRELP.

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