As the largest subunit of the nuclear remodeling factor complex,
Bromodomain PHD Finger Transcription Factor (BPTF) has been reported to be involved in
tumorigenesis and development in several
cancers. However, to date, its functions and related molecular mechanisms in
colorectal cancer (CRC) are still poorly defined and deserve to be revealed. In this study, we uncovered that, under the expression regulation of c-Myc, BPTF promoted CRC progression by targeting Cdc25A. BPTF was found to be highly expressed in CRC and promoted the proliferation and
metastasis of CRC cells through BPTF specific siRNAs, shRNAs or inhibitors. Based on
RNA-seq, combined with
DNA-pulldown, ChIP and
luciferase reporter assay, we proved that, by binding to -178/+107 region within Cdc25A promoter, BPTF transcriptionally activated Cdc25A, thus accelerating the cell cycle process of CRC cells. Meanwhile, BPTF itself was found to be transcriptionally regulated by c-Myc. Moreover, BPTF knockdown or inactivation was verified to sensitize CRC cells to chemotherapeutics,
5-Fluorouracil (
5FU) and
Oxaliplatin (Oxa), c-Myc inhibitor and cell cycle inhibitor not just at the cellular level in vitro, but in subcutaneous xenografts or AOM/DSS-induced in situ models of CRC in mice, while Cdc25A overexpression partially reversed BPTF silencing-caused
tumor growth inhibition. Clinically, BPTF, c-Myc and Cdc25A were highly expressed in CRC tissues simultaneously, the expression of any two of the three was positively correlated, and their expressions were highly relevant to
tumor differentiation, TNM staging and poor prognosis of CRC patients. Thus, our study indicated that the targeted inhibition of BPTF alone, or together with
chemotherapy and/or cell cycle-targeted
therapy, might act as a promising new strategy for CRC treatment, while c-Myc/BPTF/Cdc25A signaling axis is expected to be developed as an associated set of candidate
biomarkers for CRC diagnosis and prognosis prediction.