KDM3B promotes neural invasion in colorectal cancer through TrkA upregulation by inhibiting H3K9 dimethylation

Abstract Neural invasion (NI) represents a critical factor contributing to the unfavorable prognosis of patients diagnosed with colorectal cancer (CRC), necessitating an investigation into its underlying mechanisms. This study identifies lysine demethylase 3B (KDM3B) as a pivotal protein associated with NI in CRC, as determined through tandem mass tag sequencing (TMT-Seq) analysis of clinical CRC tissues, which involved a comparative assessment of control and NI samples. Furthermore, Cut-tag and ATAC-Seq experiments conducted on CRC cell lines (comparing control to sh-KDM3B) demonstrated that KDM3B enhances the expression of the nerve growth factor receptor NTRK1, which encodes the TrkA protein in CRC. This finding was corroborated through both in vivo and in vitro experiments. The results indicated that KDM3B overexpression in CRC results in the inhibition of H3K9me2, which subsequently leads to the upregulation of TrkA. This upregulation facilitates the binding of nerve growth factor (NGF) to TrkA, thereby promoting NI in CRC. This study elucidates the intrinsic mechanisms underlying NI in CRC and provides a robust theoretical framework for considering KDM3B as a prognostic indicator and a potential therapeutic target for the disease