目的： 探讨circAGFG1对胆管癌QBC939细胞增殖、迁移和侵袭的影响及可能机制。 方法： 收集2017年4月至2019年10月于联勤保障部队第九八八医院接受手术的 33 例胆管癌患者的癌组织及对应癌旁组织，qPCR 法检测组织中circAGFG1 和 miR-4429 表达水平。体外培养胆管癌 QBC939 细胞，分 别 转 染 si-circAGFG1 、miR-4429 mimic 、共 转 染si-circAGFG1与anti-miR-4429后，采用CCK-8法和克隆形成实验检测对细胞增殖的影响，划痕实验和Transwell法分别检测对细胞迁移和侵袭的影响，WB 法检测对细胞中 E-cadherin 和 N-cadherin 蛋白表达的影响。双荧光素酶报告基因实验验证circAGFG1 和 miR-4429 之间的靶向调控关系。 结果： 胆管癌组织中 circAGFG1 的表达量高于癌旁组织（3.89±0.26 vs 1.00±0.08，P<0.05），而miR-4429的表达量低于癌旁组织（0.28±0.03 vs 1.00±0.05，P<0.05）。干扰circAGFG1或过表达miR-4429后，QBC939细胞增殖水平、克隆形成数、划痕愈合率、侵袭细胞数及细胞中 N-cadherin 蛋白表达均显著降低（均P<0.05），而E-cadherin蛋白表达显著升高（P<0.05）。circAGFG1可靶向结合miR-4429，且干扰circAGFG1会 促 进 QBC939 细 胞 中 miR-4429表达（均P<0.05）。下调miR-4429表达能够逆转干扰circAGFG1对QBC939细胞增殖、迁移和侵袭的影响（均P<0.05）。 结论：circAGFG1在胆管癌组织中表达升高，其可能通过靶向抑制miR-4429促进胆管癌QBC939细胞的增殖、迁移和侵袭。

Objective: To investigate the effect of circAGFG1 on the proliferation, migration and invasion of cholangiocarcinoma QBC939 cells and its possible mechanism. Methods: The tumor tissues and corresponding para-cancerous tissues of 33 patients with cholangiocarcinoma who underwent surgical resection in the 988th Hospital of the Joint Logistics Support Force from April 2017 to October 2019 were collected. qPCR was used to detect the expression level of circAGFG1 and miR-4429 in the tissues. Cholangiocarcinoma QBC939 cells were cultured in vitro and transfected with si-circAGFG1 or miR-4429 mimics, or co-transfected with si-circAGFG1 and anti-miR-4429. Then, cell proliferation was detected by CCK-8 method and clone formation test, cell migration and invasion were detected by scratch test and Transwell assay, and the protein expression of E-cadherin and N-cadherin in cells was determined by Western blotting. Dual-luciferase reporter gene experiment was adopted to verify the regulatory relationship between circAGFG1 and miR-4429. Results: The expression of circAGFG1 was higher (3.89±0.26 vs 1.00±0.08, P<0.05) while the expression of miR-4429 (0.28±0.03 vs 1.00±0.05, P<0.05) was lower in cholangiocarcinoma tissues than those in para-cancerous tissues. After the interference with circAGFG1 or over-expression of miR-4429, the cell proliferation level, number of clone formation, scratch healing rate, number of invaded cells, and the protein expression of N-cadherin in QBC939 cells were reduced (all P<0.05), but the protein expression of E-cadherin was elevated (P<0.05). circAGFG1 could targetedly bind with miR-4429, and interfering circAGFG1 promoted the expression of miR-4429 in QBC939 cells (all P<0.05). Down-regulation of miR-4429 reversed the effect of interfering circAGFG1 on the proliferation, migration and invasion of QBC939 cells (all P<0.05). Conclusion: The expression of circAGFG1 is up-regulated in cholangiocarcinoma tissues, which may promote the proliferation, migration and invasion of cholangiocarcinoma QBC939 cells by targetedly inhibiting the expression of miR-4429.

R735.8；R730.2