Transcription Activation of DEPDC1B Upon EBF1 Loss Contributes to Cell Cycle Progression and Epithelial-Mesenchymal Transition in Colon Adenocarcinoma.

Grounded on bioinformatics insights, this study investigates the interaction between DEP domain containing 1B (DEPDC1B) and early B cell factor 1 (EBF1), their expression patterns, and their functions in the progression of colon adenocarcinoma (COAD). DEPDC1B was identified as a potential oncogene aberrantly expressed in COAD, and its high expression was detected in COAD cell lines. DEPDC1B silencing in COAD cell lines while blocking epithelial-mesenchymal transition (EMT), dissemination, and expansion of COAD cells in vitro. Additionally, DEPDC1B knockdown suppressed tumorigenic activity and metastasis of mouse CT26 cells in isograft tumor models. EBF1, poorly expressed in COAD, was found to repress DEPDC1B transcription. EBF1 overexpression reduced DEPDC1B expression, thus diminishing the malignant properties of cancer cells. Nevertheless, its tumor-suppressive effects were negated by DEPDC1B restoration. EBF1 presented a promoter hypermethylation pattern in COAD cell lines, in which its expression was restored upon treatment of the methylation inhibitor 5-azacytidine. In conclusion, this study highlights that the hypermethylation of EBF1 leads to transcription activation of DEPDC1B, which promotes cell cycle progression, EMT, and malignant progression in COAD. Restoring EBF1 levels or suppressing DEPDC1B expression may be promising strategies for COAD management.