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Suppression of LINC00460 mediated the sensitization of HCT116 cells to ionizing radiation by inhibiting epithelial-mesenchymal transition.
Toxicology Research ( IF 2.2 ) Pub Date : 2020-04-24 , DOI: 10.1093/toxres/tfaa010
Jiani Zhang 1 , Lixin Ding 2 , Gaofeng Sun 3 , Huacheng Ning 4 , Ruixue Huang 4
Affiliation  

Radiation resistance is the most common challenge for improving radiotherapy. The mechanisms underlying the development of radioresistance remain poorly understood. This study aims to explore the role of LINC00460 in ionizing radiation-induced radioresistance as well as the mechanisms by which LINC00460 is regulated by radiation exposure. The expression of LINC00460 was measured. Cell proliferation and colony formation were measured in HCT116 cells after treatment by radiation. The development of epithelial-mesenchymal transition (EMT) was determined with or without knockdown LINC00460 expression using western blot analysis. Transcription activity was determined using a series of LINC00460-promoter luciferase reporter gene vectors. LINC00460 expression was significantly higher in HCT116 cells, relative to other cell types, with LINC00460 expression significantly affecting HCT116 cell proliferation. Suppression of LINC00460 inhibits EMT development in HCT116 cells via regulation of ZEB1 expression. Furthermore, LINC00460 expression was induced by irradiation via the activation of c-jun transcription factor-binding element located on the LINC00460 promoter. LINC00460 was shown to play a crucial role in EMT-associated progression of colorectal cancer, indicating that LINC00460 may be an indicator or new potential therapeutic target for colorectal cancer radiosensitization.

中文翻译:

LINC00460的抑制通过抑制上皮-间质转化介导了HCT116细胞对电离辐射的敏感性。

抗辐射能力是改善放射治疗的最普遍挑战。耐辐射性发展的基本机制仍然知之甚少。这项研究旨在探讨LINC00460在电离辐射诱导的辐射抗性中的作用,以及通过辐射暴露调节LINC00460的机制。测量LINC00460的表达。通过辐射处理后,在HCT116细胞中测量细胞增殖和集落形成。上皮-间质转化(EMT)的发展确定是否有敲低LINC00460表达使用蛋白质印迹分析。使用一系列LINC00460-启动子荧光素酶报道基因载体确定转录活性。相对于其他细胞类型,LINC00460在HCT116细胞中的表达明显更高,LINC00460的表达明显影响HCT116细胞的增殖。LINC00460的抑制通过调节ZEB1表达来抑制HCT116细胞中的EMT发育。此外,通过活化位于LINC00460启动子上的c-jun转录因子结合元件,通过辐射诱导了LINC00460的表达。LINC00460被证明在大肠癌的EMT相关进展中起关键作用,这表明LINC00460可能是大肠癌放射增敏的指示剂或新的潜在治疗靶标。通过活化位于LINC00460启动子上的c-jun转录因子结合元件,通过辐照诱导LINC00460表达。LINC00460被证明在大肠癌的EMT相关进展中起关键作用,这表明LINC00460可能是大肠癌放射增敏的指示剂或新的潜在治疗靶标。通过活化位于LINC00460启动子上的c-jun转录因子结合元件,通过辐照诱导LINC00460表达。LINC00460被证明在大肠癌的EMT相关进展中起关键作用,这表明LINC00460可能是大肠癌放射增敏的指示剂或新的潜在治疗靶标。
更新日期:2020-04-24
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