HOXC9 transcriptionally activates NRP1 to promote cell malignant progression and immune evasion in colorectal cancer.

Authors

Xiaofeng Qiu, Sheng Hu, Bingling Liao, Huijun Zhang, Yuncheng Tang, Qihua Xu

Published in

Molecular genetics and genomics : MGG. Volume 301. Issue 1. Aug 25, 2026. Epub Aug 25, 2026.

Abstract

Transcription factor homeobox C9 (HOXC9) has been reported to be up-regulated and associated with poor prognosis in colorectal cancer (CRC). This study focused on the regulatory role and molecular mechanism of HOXC9 in CRC progression and immune response. Differential analysis from the GSE25070 dataset was performed. The mRNA and protein levels of target genes were measured using qPCR and Western blotting. Malignant behaviors in LoVo and Caco2 cells were assessed using colony formation assay, transwell assay and tumor sphere formation assay. Programmed death ligand 1 (PD-L1) expression on cell surface was detected using flow cytometry. LoVo and Caco2 cells were co-cultured with CD8 + T cells, followed by apoptosis detection using flow cytometry and quantification of immune-related mRNA using qPCR. Role of HOXC9 in vivo was explored through xenograft tumor assay. Interaction between HOXC9 and neuropilin 1 (NRP1) was validated via chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. HOXC9 was upregulated and predicted a poor prognosis in CRC. Silencing HOXC9 suppressed CRC cell proliferation, migration, invasion, cell stemness, down-regulated PD-L1 expression and promoted anti-tumor immune function of CD8 + T cells. HOXC9 knockdown reduced CRC tumor growth and PD-L1 expression in vivo. HOXC9 elevated NRP1 expression via transcriptional activation of NRP1. NRP1 overexpression could reverse CRC progression inhibition and immune function enhancement caused by HOXC9 downregulation. These findings elucidate a specific mechanism whereby HOXC9 transcriptionally activates NRP1, thereby contributing to CRC malignant development and immune evasion.

PMID:
42637860
Bibliographic data and abstract were imported from PubMed on 25 Aug 2026.

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