Both CHGA and UCHL1-activated transcription were regulated through the Rho/ERK/NF-κB signaling pathways by histone modifications of H3K4 trimethylation.<h4>Conclusions</h4>In this study, Rho/ERK/NFκB signaling-mediated CHGA and UCHL1 expression, which is regulated through histone modifications and affects OXA-resistant CRC EMT outcomes, was assessed, and its potential as an early detection biomarker and prognostic indicator was explored with clinical applications. The gene discussed is RHO; the disease is colorectal carcinoma.