ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF‑κB signaling pathway.

Abstract

Zinc finger and BTB domain containing 7A (ZBTB7), a POZ/BTB and Krüppel erythroid myeloid oncogenic factor, is critical for the tumorigenicity and progression of various cancer types. ZBTB7 has been reported to promote the cell proliferation of colorectal cancers (CRC). However, the function of ZBTB7 to 5-fluorouracil (5‑FU) resistance has not yet been studied. In the current study, ZBTB7 expression and function in 5‑FU resistance in CRC were investigated using with multidisciplinary approaches, including western blot analysis, Transwell assay, CCK8 and a tumor xenograft model. Overexpression of ZBTB7 was increased the level of proteins associated with cell invasion and epithelial-mesenchymal transition. ZBTB7 inhibition attenuated the invasion and enhanced the apoptosis of CRC cells. IC50 values and cell viability were significantly reduced in cells with short hairpin RNA (shRNA)-mediated ZBTB7 depletion compared with the control group. 5‑FU administration decreased viability to a greater extent in the ZBTB7-shRNA group compared with the control, which was dose- and time-dependent. Analysis of gene expression omnibus data demonstrated that ZBTB7 mediated 5‑FU resistance, potentially through nuclear factor (NF)-κB signaling. NF‑κB inhibitor SN50 reversed ZBTB7-induced resistance in CRC. Collectively, the findings demonstrated that ZBTB7 mediated 5‑FU resistance in CRC cells through NF‑κB signaling. Thus, targeting ZBTB7 and NF‑κB signaling may be an effective strategy to reverse 5‑FU resistance in CRC.