Trpa1 knockout favors colon tumorigenesis in dextran sulfate sodium (DSS)-induced colitis mice.

Abstract

Chronic inflammation in the colon has been recognized as a key pathogenic mechanism driving colorectal cancer development. TRPA1 (transient receptor potential ankyrin 1), a key member of the TRP cation channel superfamily, is closely implicated in inflammatory processes and has emerged as a promising therapeutic target for anti-inflammatory drug development. However, the precise role of TRPA1 in colorectal carcinogenesis and its potential as a therapeutic target for colorectal cancer (CRC) remain incompletely understood. In this study, we demonstrate that Trpa1 knockout significantly exacerbates DSS-induced colitis-associated tumorigenesis in murine models, a phenomenon mechanistically linked to Trpa1 deficiency-mediated aggravation of inflammatory bowel pathology. RNAseq and gene knockout effect analysis revealed a consistently low expression pattern of TRPA1 across colorectal cancer cell lines (n = 58, median log2(TPM+1) = 0.025), with limited impact on cell viability upon TRPA1 knockout. Notably, analysis of human clinical specimens revealed substantial downregulation of TRPA1 expression in CRC compared to adjacent normal tissues. Kaplan-Meier survival analysis further indicated that patients with TRPA1-low tumors exhibited significantly poorer overall survival outcomes. These collective data suggest a tumor-suppressive role for TRPA1 in colorectal carcinogenesis, potentially through its immunomodulatory functions within the colitis-cancer transformation axis.