Mesalazine Regulates DUSP1, DUSP4, and DUSP5 Expression in Colorectal Cancer: In Vitro and Bioinformatic Evidence

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with its development closely linked to dysregulation of mitogen-activated protein kinase (MAPK) signaling pathways. <b>Background</b>: Dual-specificity phosphatases (DUSPs), as key regulators of MAPKs, play a crucial role in maintaining the balance between proliferation and apoptosis. <b>Methods</b>: In this study, we investigated the effect of mesalazine (MES) on the expression and activity of selected DUSP family members in normal colon epithelial cells (CCD-841CoN) and colorectal cancer cells (DLD-1). <b>Results</b>: Microarray analysis identified 24 transcripts with altered expression upon mesalazine treatment. The number of significantly regulated genes decreased with increasing fold-change (FC) thresholds, from 20 genes (FC > 1.1) to 13 (FC > 1.5) and 5 (FC > 2.0), all with <i>p</i> < 0.001. Among the <i>DUSP</i> genes, <i>DUSP4</i> and <i>DUSP5</i> showed the most pronounced and cell-type-dependent modulation. Mesalazine upregulated <i>DUSP4</i> and <i>DUSP5</i> expression in DLD-1 cells (<i>p</i> < 0.001), while reducing their expression in normal CCD-841CoN cells. ELISA confirmed a 1.56-fold increase in DUSP5 protein concentration in mesalazine-treated cancer cells compared with controls (<i>p</i> < 0.001). <b>Conclusions</b>: These findings suggest that mesalazine differentially modulates <i>DUSP</i> gene expression in normal and malignant colon epithelial cells, potentially contributing to its antiproliferative and pro-apoptotic effects through the regulation of MAPK signaling. These results provide new insights into the molecular mechanisms underlying the anticancer effects of mesalazine in colorectal cancer.