ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF-κB signaling pathway
ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF-κB signaling pathway
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DOI：
10.3892/ijo.2018.4521
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发表时间：
2018-11-01
影响因子：
5.2
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
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作者：
Wang, Zexin;Zhao, Xilan;Zhou, Qi
含有7A的锌指和BTB结构域(ZBTB7)是一种POZ/BTB和Kruppel红系髓系癌基因因子，在各种类型的癌症的发生和发展中起关键作用。据报道，ZBTB7可促进结直肠癌(CRC)的细胞增殖。然而，ZBTB7在5-氟尿嘧啶(5-FU)耐药中的作用尚未得到研究。本研究采用免疫印迹分析、Transwell法、CCK8和肿瘤移植瘤模型等多学科方法，研究ZBTB7在结直肠癌5-FU耐药中的表达和作用。ZBTB7的过表达增加了与细胞侵袭和上皮-间充质转化相关的蛋白水平。抑制ZBTB7可抑制大肠癌细胞的侵袭，促进细胞的凋亡。在短发夹状RNA(ShRNA)介导的ZBTB7缺失的细胞中，IC50值和细胞活力与对照组相比显著降低。与对照组相比，ZBTB7-shRNA组5-FU给药对细胞存活率的影响更大，且呈剂量和时间依赖性。基因表达综合数据分析表明，ZBTB7可能通过核因子B信号途径介导5-FU耐药。核因子-B抑制剂SN50逆转ZBTB7诱导的结直肠癌耐药。综上所述，这些结果表明ZBTB7通过核因子-B信号转导5-FU耐药。因此，靶向ZBTB7和NF-B信号通路可能是逆转结直肠癌5-FU耐药的有效策略。
Zinc finger and BTB domain containing 7A (ZBTB7), a POZ/BTB and Kruppel erythroid myeloid onco-genic 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)-B signaling. NF-B inhibitor SN50 reversed ZBTB7-induced resistance in CRC. Collectively, the findings demonstrated that ZBTB7 mediated 5-FU resistance in CRC cells through NF-B signaling. Thus, targeting ZBTB7 and NF-B signaling may be an effective strategy to reverse 5-FU resistance in CRC.