项目名称: 炎症作用下circ_0007986/miRNA调控食管癌细胞耐药促进肿瘤转移机制研究
项目编号: No.81672415
项目类型: 面上项目
立项/批准年度: 2017
项目学科: 医药、卫生
项目作者: 王铭辉
作者单位: 中山大学
项目金额: 25万元
中文摘要: 化疗耐药严重影响食管癌治疗效果,阐明食管癌化疗耐受至关重要。自噬是肿瘤产生耐药的重要原因,非编码RNA在多种肿瘤中调控化疗耐药和自噬并促转移,circRNA是一种新型非编码RNA,其在肿瘤进展中作用与机制备受关注。本课题预实验结果显示circ_0007986在食管癌化疗耐受合并脑转移组织及耐药细胞系中高表达,生物信息学提示circ_0007986与miR-7-5p有结合位点。干扰circ_0007986表达能显著抑制食管癌细胞运动能力,表明circ_0007986高表达和食管癌耐药转移密切相关。本课题将进一步阐明circ_0007986/miRNA结合关系,揭示circRNA/miRNA互作调控食管癌耐药促转移的分子机理。本研究将有助于揭示circRNA/miRNA参与调控肿瘤细胞生物学的分子机制,并为靶向circRNA/miRNA治疗食管癌耐药转移药物开发提供理论依据。
中文关键词: 食管癌;化疗耐药;环状RNA;小RNA;自噬
英文摘要: Chemoresistance severely impaired the efficacy of chemotherapy of esophageal cancer and it is very important to illustrate the mechanism of chemoresistance. Autophagy has been believed to contributes a lot to tumor chemoresistance. Meanwhile, Non-coding RNAs play very important roles in chemoresistance and metastasis. As a novel type of non-coding RNA, the function and mechanism of circRNAs in tumorigenesis attracted much attention. From our previous data, we found that circ_0007986 is overexpressed in chemoresistant and brain metastasis esophageal cancer. Furthermore, there are binding sites between circ_0007986 and miR-7-5p. Downregulation of circ_0007986 can severely suppress esophageal cancer cell migration and invasion, implying the association between circ_0007986 and chemoresistance. In the following experiments, we will confirm the binding between circ_0007986 and miR-7-5p. Moreover, we will also explore the chemoresistance and metastasis mechanism regulated by circRNA/miRNA. Our study not only can contribute to illustrate the regulatory mechanism of circRNA/miRNA, which promotes esophageal cancer chemoresistance and metastasis; but also provide a new molecular therapy of targeting to the circRNA/miRNA in esophageal cancer.
英文关键词: esophageal cancer ;chemoresistence;circRNA;miRNA;autophagy