TY - JOUR AB - Besides being a key contributor to epithelial‑to‑mesenchymal transition (EMT) activation and stemness maintenance, zinc finger E-box binding homeobox 1 (ZEB1) is also a crucial inducer of chemoresistance and radioresistance. Unlike the clear mechanism that mediates its effect on EMT and dedifferentiation, the mechanism of how ZEB1 promotes chemo- and radio-resistance remains to be elucidated. It has been previously reported that ZEB1 promotes DNA double-strand break clearance by enhancing the deubiquitylating activity of ubiquitin-specific peptidase (USP)7 on checkpoint kinase 1, which is an important step during DNA repair. It was hypothesized that as a transcriptional suppressor, ZEB1 may be involved in an unbalanced DNA damage response (DDR) by affecting other key components. Therefore, in the present study, the target gene occupancy of ZEB1 was mapped in colorectal cancer cells using the ChIP-on-chip method, revealing positive intervals enriched along the three DDR-associated genes: USP17, chromodomain helicase DNA-binding protein 1-like and double homeobox 4. The E-boxes identified in the binding regions and the enhanced mRNA expression of the three genes following the knockdown of ZEB1 supported the identification of these three genes as downstream target genes of ZEB1. Furthermore, ZEB1 knockdown initiated a chemosensitization effect, induced G1/S arrest and increased apoptosis, which functionally validated the three ZEB1 downstream targets. In summary, the present study identified three DDR-associated genes as ZEB1 downstream targets, and demonstrated that their suppression by ZEB1 contributes to ZEB1-mediated chemoresistance. AD - College of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P.R. China Collaborative Innovation Center of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P.R. China AU - Wang,Miao AU - He,Su-Fei AU - Liu,Lei-Lei AU - Sun,Xiao-Xia AU - Yang,Fan AU - Ge,Qian AU - Wong,Wei-Kang AU - Meng,Jing-Yan DA - 2017/10/01 DO - 10.3892/or.2017.5888 EP - 1948 IS - 4 JO - Oncol Rep KW - zinc finger E-box binding homeobox 1 DNA damage response DNA repair promoter profiling chemoresistance ubiquitin-specific peptidase 17 chromodomain helicase DNA-binding protein 1-like double homeobox 4 PY - 2017 SN - 1021-335X 1791-2431 SP - 1941 ST - Potential role of ZEB1 as a DNA repair regulator in colorectal cancer cells revealed by cancer-associated promoter profiling T2 - Oncology Reports TI - Potential role of ZEB1 as a DNA repair regulator in colorectal cancer cells revealed by cancer-associated promoter profiling UR - https://doi.org/10.3892/or.2017.5888 VL - 38 ER -