| 罗加林,刘鲁迎,沈金闻.miR-519b-3p表达与局部晚期直肠癌患者术前放化疗应答的相关性及机制研究[J].肿瘤学杂志,2019,25(7):627-633. |
| miR-519b-3p表达与局部晚期直肠癌患者术前放化疗应答的相关性及机制研究 |
| Relationship Between Expression of MicroRNA-519b-3p and Preoperative Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer and Its Mechanism |
| 投稿时间：2019-03-31 |
| DOI：10.11735/j.issn.1671-170X.2019.07.B008 |
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| 中文关键词: 局部晚期直肠癌 术前同步放化疗 miR-519b-3p ARID4B |
| 英文关键词:Locally advanced rectal cancer preoperative concurrent chemoradiotherapy miR-519b-3p ARID4B |
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| 中文摘要: |
| 摘 要：［目的］ 研究miR-519b-3p表达与局部晚期直肠癌术前放化疗应答的相关性，并探讨miR-519b-3p是否通过靶向作用ARID4B提高局部晚期直肠癌患者术前放化疗的反应性。［方法］ 实时定量PCR检测局部晚期直肠癌患者miR-519b-3p的表达水平，用miR-519b-3p模拟物或抑制剂转染HCT116或SW480细胞，体外验证其表达水平与放化疗反应的相关性；双荧光素酶报告实验用于检测miR-519b-3p与ARID4B之间的相互作用；通过重组质粒构建及细胞转染调节相关基因在细胞内的表达，通过建立裸鼠异位移植瘤模型，在体验证miR-519b-3p对ARID4B的调节作用。［结果］ 实验发现miR-519b-3p表达与局部晚期直肠癌患者对pCRT的反应性相关，miR-519b-3p在局部晚期直肠癌应答患者中呈现为高表达。miR-519b-3p的过表达增强了体外放化疗的反应性。在机理上，我们发现miR-519b-3p直接与ARID4B mRNA的3′UTR结合，其表达与miR-519b-3p表达呈负相关。功能实验显示miR-519b-3p以ARID4B依赖方式直接与直肠癌患者对术前放化疗的反应密切相关。［结论］ miR-519b-3p通过靶向作用ARID4B提高局部晚期直肠癌患者术前放化疗的反应性。 |
| 英文摘要: |
| Abstract：［Purpose］ To study the correlation between the expression of microRNA-519b-3p and preoperative response to chemoradiotherapy in locally advanced rectal cancer，and to explore whether microRNA-519b-3p can improve preoperative response to chemoradiotherapy in locally advanced rectal cancer patients by targeting ARID4B. ［Methods］ Real-time quantitative PCR was used to detect the expression of microRNA-519b-3p in patients with locally advanced rectal cancer. HCT116 or SW480 cells were transfected with mimic or inhibitor of microRNA-519b-3p. The correlation between the expression level and the response chemoradiotherapy was verified in vitro. Dual luciferase reporter assay was used to detect the interaction between microRNA-519b-3p and ARID4B. The related genes were regulated by recombinant plasmid and cell transfection. In vivo，the regulatory effect of microRNA-519b-3p on ARID4B was validated by establishing heterotopic xenograft tumor model in nude mice. ［Results］ It was found that the expression of microRNA-519b-3p was correlated with the responsiveness of LARC patients to pCRT. The expression of microRNA-519b-3p was high in LARC responders. Overexpression of microRNA-519b-3p enhances the responsiveness of chemoradiotherapy in vitro. In terms of mechanism，we found that microRNA-519b-3p directly bound to the 3′UTR of ARID4B，whose expression was negatively correlated with the expression of microRNA-519b-3p.Finally，functional experiments showed that miR-519b-3p was directly related to the response of rectal cancer patients to pCRT in an ARID4B-dependent manner.［Conclusion］ Mir-519b-3p improves preoperative response to chemoradiotherapy in patients with locally advanced rectal cancer by targeting ARID4B. |
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