The study investigates the role of CNTN3 in colorectal cancer (CRC) progression and its transcriptional regulation by PRRX2, exploring their potential contributions to epithelial-to-mesenchymal transition (EMT) and metastasis. Bioinformatics analysis of CRC datasets identified differentially expressed genes. CNTN3 expression was validated using qPCR, Western blotting, and immunohistochemistry. Functional assays, including cell proliferation, apoptosis, migration, and invasion assays, as well as the detection of EMT markers, assessed the oncogenic role of CNTN3. Chromatin immunoprecipitation and dual-luciferase assays were performed to examine PRRX2-mediated transcriptional regulation of CNTN3. Knockdown and rescue experiments elucidated the functional interplay between PRRX2 and CNTN3. Xenograft tumors were generated for in vivo verification. CNTN3 expression was significantly elevated in CRC tissues and cell lines, correlating with tumor metastasis and advanced clinical stages. CNTN3 promoted CRC cell proliferation, inhibited apoptosis, and enhanced EMT, migration, and invasion in vitro. PRRX2 was found to bind to the CNTN3 promoter. PRRX2 knockdown reduced CNTN3 expression, reversed EMT marker alterations, and suppressed metastatic phenotypes. These findings suggest that the PRRX2-CNTN3 axis may serve as a key mechanism driving CRC malignancy. This study indicates that CNTN3 functions as a putative oncogene in CRC, with its expression regulated by PRRX2, providing mechanistic insights into EMT and metastasis. The PRRX2-CNTN3 axis emerges as a potential therapeutic target for mitigating CRC progression.
Yu et al. (Wed,) studied this question.