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

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.

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。

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。非编码RNA在多种肿瘤中调控化疗耐药并促转移，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。干扰circ_0007986表达能显著抑制食管癌细胞运动能力，表明circ_00079 86高表达和食管癌耐药转移密切相关，本研究将有助于揭示circ_0007986参与调控肿瘤细胞生物学的分子机制，并为靶向circRNA治疗食管癌耐药转移药物开发提供理论依据。.我们利用Rnase R及环状测序，进一步确定circ_0007986的环状结构。利用原位杂交来检测食管癌组织及细胞系中circ_0007986的定位，我们发现circ_0007986主要定位在细胞胞浆。通过临床数据分析，我们发现circ_0007986在食管癌中高表达并且表达越高，食管癌病人生存预后越差。在机制方面我们发现circ_0007986能够增加GSK3β蛋白的磷酸化来调控Wnt通路蛋白，上调β-cateninde 蛋白水平，影响下游蛋白水平的变化来促进食管癌的发生发展。.我们的研究表明，circ_0007986可能通过上调Wnt通路蛋白表达来促进食管癌的恶性进展，这一发现为有效治疗食管癌提供了新的治疗靶点。