Integrative multi-omics analysis decodes HOXC9-driven malignant transformation and metastasis in OSCC

  • iScience. 2025 Sep 10;28(9):112919. doi: 10.1016/j.isci.2025.112919.
Mengyu Xu  1  2 ,  Zewen Sun  1  3 ,  Dandan Wang  1  4 ,  Guoxin Li  1  2 ,  Wei Feng  5  6 ,  Chunyan Qiao  4 ,  Ce Shi  4 ,  Qilin Liu  7 ,  Peng Chen  3  5  6 ,  Zhengwen An  1  2
Affiliations
  • 1. Department of Oral Biomedicine, School & Hospital of Stomatology, Jilin University, Changchun, China.
  • 2. Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School & Hospital of Stomatology, Jilin University, Changchun, China.
  • 3. Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, China.
  • 4. Department of Oral Pathology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School & Hospital of Stomatology, Jilin University, Changchun, China.
  • 5. Department of Pathology, College of Basic Medical Sciences, Jilin University, Changchun, China.
  • 6. Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China.
  • 7. Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Jilin University, Changchun, China.
PMID: 41054515 DOI: 10.1016/j.isci.2025.112919
Abstract

Oral squamous cell carcinoma (OSCC) is a highly prevalent head and neck malignancy with a poor prognosis, often exhibiting resistance to conventional therapies. This highlights an urgent need for reliable biomarkers to facilitate early detection and effective management of recurrent or metastatic cases. Leveraging multi-omics analysis, we identified the HOX gene family as significantly overexpressed and closely associated with OSCC progression. Among these, HOXC9 was prioritized as a key regulator using machine learning algorithms. Mechanistic investigations revealed a strong correlation between HOXC9 expression and DNA hypomethylation at the CDX1 motif, which play a crucial role in regulating MMP13 expression. Single-cell RNA Sequencing further elucidated the role of HOXC9 in driving OSCC malignant transformation. Clinical evidence demonstrates that HOXC9 promotes OSCC invasion and metastasis through the ITGA6/PI3K/Akt/MMP13 signaling axis. Additionally, HOXC9 expression appears to be modulated by miR-196, presenting a potential target for therapeutic intervention in OSCC.

Keywords
Bioinformatics; Cancer; Integrative aspects of cell biology; Transcriptomics.
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