MiroRNA-127-3p targets XRCC3 to enhance the chemosensitivity of esophageal cancer cells to a novel phenanthroline-dione derivative
MiroRNA-127-3p targets XRCC3 to enhance the chemosensitivity of esophageal cancer cells to a novel phenanthroline-dione derivative
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MiroRNA-127-3p 靶向 XRCC3 以增强食管癌细胞对新型菲咯啉二酮衍生物的化疗敏感性
DOI：
10.1016/j.biocel.2016.08.026
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Yu Yongchun
中科院分区：
文献类型：
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作者：
Zhen Ni;Yang Qingyuan;Zheng Kangdi;Han Zeping;Sun Fenyong;Mei Wenjie;Yu Yongchun
MicroRNA是一种长度为18-22个核苷酸的非编码小RNA，通过3′端非翻译区靶向基因转录后降解，参与多种生物学过程。此外，它们已被建议改善一组肿瘤中的化学敏感性。然而，microRNA-127- 3 p在食管癌发生中的生物学功能仍然是个谜。因此，本研究首次分析了microRNA-127- 3 p在体外和体内对食管癌细胞生长的调控作用。随后，使用microRNA靶向基因预测软件和双荧光素酶报告基因测定，我们证实microRNA-127- 3 p在mRNA和蛋白水平上特异性地降低了中国仓鼠细胞3（RAD 51重组酶旁系同源物之一）中X射线修复互补缺陷修复的表达。此外，使用同源重组修复和非同源末端连接修复报告系统，我们发现microRNA-127- 3 p特异性损害同源重组修复，并显着增加细胞中的DNA双链断裂。此外，它在统计学上增加了食管癌细胞对一种新的菲咯啉二酮衍生物的体内化学敏感性，通过机械地削弱RAD 51向损伤部位的募集。总之，我们的研究结果不仅表明microRNA-127- 3 p可以作为评估食管癌发展的预测因子，而且还表明它可以用于增加食管癌患者对菲咯啉二酮衍生物的化疗敏感性，菲咯啉二酮衍生物可能是未来潜在的抗癌候选物。
MicroRNAs are small non-coding RNAs with 18–22 nucleotides in length and have been proposed to function in various biological processes by targeting genes for post-transcriptional degradation via their 3′ untranslated region. Moreover, they have been suggested to improve the chemosensitivity in a panel of tumors. However, the biological functions of microRNA-127-3p in esophageal carcinogenesis are still enigmatic. Thus, in the study, we firstly analyzed the roles of microRNA-127-3p in regulating the growth of esophageal cancer cells bothin vitroandin vivo. Afterwards, using the microRNA-targeted gene prediction software and the dual-luciferase reporter assays, we confirmed that microRNA-127-3p specifically reduced the expression of X-ray repair complementing defective repair in Chinese hamster cells 3, one of RAD51 recombinase paralogs, at both mRNA and protein levels. Furthermore, using the homologous recombination repair and non-homologous end joining repair reporter systems, we found that microRNA-127-3p specifically compromised the homologous recombination repair and significantly increased DNA double strand breaks in cells. Besides, it statistically increased the chemosensitivity of esophageal cancer cells to a novel phenanthroline-dione derivativein vivoby mechanistically impairing the recruitment of RAD51 to the damage sites. In summary, our findings not only suggest that microRNA-127-3p can be used as a predictor for evaluating the development of esophageal carcinoma, but also show that it can be used to increase the chemosensitivity of esophageal cancer patients to the phenanthroline-dione derivative, which might be a potential anticancer candidate in the future.