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Peer-reviewedCC BY 4.0Experimental and Molecular Medicine

CTCF-associated chromatin changes between HOXD1 and HOXD8 contribute to TNBC progression

  • Ji Hoon Oh1
  • Da Som Jeong2,3
  • Clara Yuri Kim4
4 affiliations
  1. 1Department of Biological Sciences, Keimyung University College of Natural Sciences, Daegu, Republic of Korea
  2. 2Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
  3. 3Yonsei Institute for Digital Health, Yonsei University, Seoul, Republic of Korea
  4. 4Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
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Abstract

Homeobox (HOX) genes and their encoded DNA-binding homeoproteins are important regulators of developmental processes and have been implicated in cancer pathogenesis. Here, we investigated the roles of HOXD1 and HOXD8 across different molecular subtypes of human breast cancer (BC) using a combination of in silico analyses of large-scale patient datasets, in vitro RNA interference (RNAi) phenotyping, and in vivo validation studies. Expression levels of HOXD1 and HOXD8 were differentially altered across BC subtypes and were specifically reduced in the aggressive triple-negative breast cancer (TNBC) subtype. Functional analyses demonstrated that reduced HOXD1 and HOXD8 expression was linked to enhanced invasive, migratory, and proliferative phenotypes. In addition, our molecular analyses suggest that CCCTC-binding factor (CTCF)-associated chromatin changes and DNA methylation status at the HOXD locus contribute to coordinated regulation of HOXD1 and HOXD8 expression in BC cells. Collectively, our findings support a potential tumor-suppressive role for HOXD1 and HOXD8 in TNBC and suggest that the HOXD1/HOXD8 regulatory axis has biological and therapeutic relevance in aggressive BC.

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Cite

BibTeXRIS
BibTeX
@article{oh2026ctcfassociated,
  title = {{CTCF-associated chromatin changes between HOXD1 and HOXD8 contribute to TNBC progression}},
  author = {Ji Hoon Oh and Da Som Jeong and Clara Yuri Kim},
  journal = {Experimental and Molecular Medicine},
  year = {2026},
  month = oct,
  doi = {10.1038/s12276-026-01861-6},
  url = {https://doi.org/10.1038/s12276-026-01861-6},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - CTCF-associated chromatin changes between HOXD1 and HOXD8 contribute to TNBC progression
AU  - Ji Hoon Oh
AU  - Da Som Jeong
AU  - Clara Yuri Kim
PY  - 2026
DA  - 2026/10/01
JO  - Experimental and Molecular Medicine
DO  - 10.1038/s12276-026-01861-6
UR  - https://doi.org/10.1038/s12276-026-01861-6
AB  - Homeobox (HOX) genes and their encoded DNA-binding homeoproteins are important regulators of developmental processes and have been implicated in cancer pathogenesis. Here, we investigated the roles of HOXD1 and HOXD8 across different molecular subtypes of human breast cancer (BC) using a combination of in silico analyses of large-scale patient datasets, in vitro RNA interference (RNAi) phenotyping, and in vivo validation studies. Expression levels of HOXD1 and HOXD8 were differentially altered across BC subtypes and were specifically reduced in the aggressive triple-negative breast cancer (TNBC) subtype. Functional analyses demonstrated that reduced HOXD1 and HOXD8 expression was linked to enhanced invasive, migratory, and proliferative phenotypes. In addition, our molecular analyses suggest that CCCTC-binding factor (CTCF)-associated chromatin changes and DNA methylation status at the HOXD locus contribute to coordinated regulation of HOXD1 and HOXD8 expression in BC cells. Collectively, our findings support a potential tumor-suppressive role for HOXD1 and HOXD8 in TNBC and suggest that the HOXD1/HOXD8 regulatory axis has biological and therapeutic relevance in aggressive BC.
SN  - 2092-6413
SN  - 1226-3613
ER  -