Demethylated miR-184 regulates EPB41L5 and downregulates Notch signaling to inhibit metastasis in colorectal cancer

Abstract

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with metastasis being a major contributor to poor prognosis. MicroRNA-184 (miR-184) has been implicated in the progression of various cancers, but its role in CRC metastasis remains poorly defined. This study investigated the effects of miR-184 promoter demethylation on EPB41L5 expression and Notch signaling in CRC. SW620 human colon carcinoma cells were treated with the DNA methylation inhibitor 5-Aza for 96 h. Methylation status was assessed via bisulfite sequencing, and gene expression was evaluated using qRT-PCR and Western blotting. Functional assays were conducted to assess cell proliferation, apoptosis, migration, and invasion. 5-Aza treatment significantly decreased miR-184 promoter methylation, leading to increased miR-184 expression. This upregulation suppressed CRC cell migration and invasion, induced G2/M cell cycle arrest, and promoted apoptosis. Mechanistically, miR-184 inhibited EPB41L5 expression, thereby downregulating the Notch signaling pathway and modulating epithelial–mesenchymal transition markers. High EPB41L5 expression in CRC tissues was associated with worse prognosis. These findings suggest that demethylated miR-184 inhibits CRC metastasis by targeting the EPB41L5/Notch signaling axis. This regulatory pathway may serve as a novel prognostic biomarker and therapeutic target, with potential clinical implications for the prevention and treatment of metastatic colorectal cancer.