HOXC8-activated TRIM22/NF-κB pathway promotes stemness in colorectal cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Colorectal cancer (CRC) presents a major global health burden with high incidence and mortality.
• The role of the HOXC8 homeobox gene in CRC proliferation and stemness is not well understood.
• Cancer stem cells drive tumor initiation, metastasis, and treatment resistance.

Purpose of the Study:

• To investigate the functional role of HOXC8 in colorectal cancer.
• To elucidate the molecular mechanisms by which HOXC8 influences CRC progression and stemness.
• To identify potential therapeutic targets for CRC treatment.

Main Methods:

• Assessed the impact of HOXC8 overexpression on CRC cell proliferation, stemness, and chemoresistance.
• Investigated the downstream targets of HOXC8, including TRIM22.
• Analyzed the involvement of the NF-κB signaling pathway in HOXC8-mediated effects.

Main Results:

• HOXC8 overexpression significantly increased CRC cell proliferation, stemness properties, and chemoresistance.
• HOXC8 was found to transcriptionally activate TRIM22.
• TRIM22 mediated the ubiquitination and degradation of IκBα, leading to NF-κB pathway activation and stemness maintenance.

Conclusions:

• HOXC8 promotes CRC progression by enhancing proliferation, stemness, and chemoresistance.
• A novel signaling axis, HOXC8/TRIM22/NF-κB, was identified as a key regulator of stemness in CRC.
• Targeting the HOXC8/TRIM22/NF-κB pathway may offer a promising therapeutic strategy for colorectal cancer.