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

Since neural invasion (NI) is a key factor leading to poor prognosis of patients with colorectal cancer (CRC), exploring its mechanism in CRC is an urgent challenge. In this study, lysine demethylase 3B (KDM3B), a differential protein for NI in CRC, was detected by TMT-seq of clinical CRC tissues (control vs. NI). Cut-tag and ATAC-seq of CRC cell line (control vs. sh-KDM3B) found that KDM3B promoted the expression of TrkA-encoding sequence NTRK1 in CRC, which was then verified through <i>in vivo</i> and <i>in vitro</i> experiments. The results demonstrated that overexpression of KDM3B in CRC could inhibit H3K9me2, which in turn contributed to the upregulation of TrkA, enabling binding of nerve growth factor (NGF) to it and ultimately inducing CRC NI. The present study reveals the intrinsic mechanism of NI in CRC, which lays a solid theoretical foundation for using KDM3B as a prognostic indicator and therapeutic target for CRC.