Immune-driven induction of miR-501-5p by IL-17A enhances colorectal cancer progression.

BACKGROUND

Colorectal cancer (CRC) patients are more susceptible to infections due to immune dysregulation. The interleukin-17A (IL-17A) signaling pathway plays a critical role in both immune defense and cancer metastasis. This study aimed to identify novel microRNAs (miRNAs) involved in IL-17A-mediated CRC progression.

METHODS

RNA sequencing (RNA-seq) was used to analyze gene expression in stimulated peripheral blood mononuclear cells (PBMCs) and HCT116 cells cultured with their conditioned media (CM). Candidate miRNAs involved in IL-17A or transforming growth factor-β (TGF-β)-driven CRC progression were evaluated by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), western blotting, and wound healing assays. Prognostic relevance was assessed in The Cancer Genome Atlas colon adenocarcinoma (TCGA-COAD) cohort via Cox regression and Kaplan-Meier survival analysis.

RESULTS

IL-17 signaling emerged as one of the most significantly enriched pathways following immune stimulation. Both IL-17A and TGF-β upregulated the epithelial-mesenchymal transition (EMT) marker vimentin and promoted CRC cell migration. Among the five candidate miRNAs identified, miR-501-5p was markedly induced by IL-17A and TGF-β. Functional assays revealed that either transient overexpression or inhibition of miR-501-5p significantly altered CRC cell migration in response to IL-17A. Notably, elevated miR-501 expression was associated with more than a twofold increased risk of death in stage IV CRC patients from the TCGA-COAD cohort.

CONCLUSIONS

IL-17 signaling may drive CRC progression and poor clinical outcomes in part through the induction of miR-501-5p, underscoring its potential role in immune-related cancer metastasis and as a prognostic biomarker.