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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Oral squamous cell carcinoma (OSCC) presents a significant global health challenge due to its high prevalence and poor patient outcomes.
• Resistance to current treatments necessitates the discovery of novel biomarkers for early detection and management of OSCC recurrence and metastasis.

Purpose of the Study:

• To identify novel molecular targets for oral squamous cell carcinoma (OSCC) therapy.
• To elucidate the role of the HOX gene family, specifically HOXC9, in OSCC progression and metastasis.

Main Methods:

• Multi-omics analysis and machine learning algorithms were employed to identify key regulatory genes in OSCC.
• Mechanistic studies, including single-cell RNA sequencing, investigated the functional role of HOXC9.
• Analysis of signaling pathways, DNA methylation, and microRNA interactions was performed.

Main Results:

• The HOX gene family, particularly HOXC9, was found to be significantly overexpressed in OSCC.
• HOXC9 promotes OSCC invasion and metastasis via the ITGA6/PI3K/Akt/MMP13 signaling axis.
• HOXC9 expression correlates with DNA hypomethylation of the CDX1 motif, influencing MMP13 regulation, and is modulated by miR-196.

Conclusions:

• HOXC9 is a critical driver of OSCC malignant transformation, invasion, and metastasis.
• HOXC9 represents a potential therapeutic target for OSCC, with miR-196 as a possible modulator.