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

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

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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