CRISPR/Cas9‑mediated claudin‑2 knockout in HCT116 cells reveals its key role in colorectal cancer progression

Colorectal cancer (CRC) progression involves complex mechanisms of invasion and metastasis. Claudin-2 (<i>CLDN2</i>), a tight junction protein, has emerged as a key regulator paracellular permeability and its dysregulation is implicated in chronic inflammatory diseases and cancer. The present study aimed to determine the mechanisms by which <i>CLDN2</i> deletion affects genes associated with motility and invasion of colon cancer cells. CRISPR/Cas9 was used to knock out <i>CLDN2</i> in HCT116 cells. Subsequently, gene expression was analyzed using reverse transcription-quantitative PCR and migratory capacity was assessed using wound healing assays. <i>CLDN2</i> deletion led to the downregulation of genes associated with motility and metastasis, including zonula occludens-1-associated nucleic acid binding protein, N-Myc downstream-regulated gene 1, <i>CLDN14, CLDN23, Bcl-2, p53</i> and <i>Bcl-6</i>, suggesting that <i>CLDN2</i> supports pro-migratory gene networks. These findings demonstrated that <i>CLDN2</i> regulates metastatic gene expression in CRC. Although further mechanistic studies are warranted, the present study provided notable genetic and phenotypic evidence of the role of <i>CLDN2</i> in promoting cancer cell migration and invasion, offering a potential foundation for future studies into its signaling interactions and therapeutic potential.