机构地区:[1]浙江大学医学院附属金华医院全科医学科,浙江省金华市321000
出 处:《世界华人消化杂志》2024年第8期608-615,共8页World Chinese Journal of Digestology
摘 要:背景胃癌是常见的消化道肿瘤,具有较高的发病率和死亡率.环状RNAs(circular RNAs,circRNAs)被认为是多种人类癌症进展的关键调控子,包括胃癌.研究显示circRASSF2作为促癌因子调控癌症进程.然而其在胃癌进展中的作用及潜在分子机制尚不清楚.目的探讨circRASSF2影响胃癌细胞增殖、迁移和凋亡的分子机制.方法用实时荧光定量PCR分析胃癌组织、癌旁组织及GES-1、HGC-27和AGS细胞中circRASSF2和miR-218-5p的表达;双荧光素酶报告实验分析靶向关系;将HGC-27和AGS细胞分为si-circRASSF2组、si-NC组、miR-218-5p mimic组、miR-NC组、si-circRASSF2+anti-miR-NC组、si-circRASSF2+miR-218-5p Inhibitor组;3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐检测细胞抑制率;克隆形成实验检测克隆形成数;流式细胞术检测细胞凋亡率;Transwell检测细胞迁移数.结果胃癌组织中circRASSF2表达上升,miR-218-5p表达下降,且二者表达呈负相关(P<0.05);在胃癌HGC-27和AGS细胞中,circRASSF2表达上调,而miR-218-5p表达下调(P<0.05).circRASSF2靶向调控miR-218-5p;敲低circRASSF2或过表达miR-218-5p促进HGC-27和AGS细胞抑制率和凋亡率,而降低克隆形成数和迁移细胞数(P<0.05).下调miR-218-5p可逆转circRASSF2敲低对细胞增殖、迁移、凋亡的影响.结论circRASSF2通过靶向miR-218-5p加速胃癌细胞增殖、迁移、抑制凋亡.BACKGROUND Gastric cancer is a common digestive tract tumor with high morbidity and mortality.Circular RNAs(circRNAs)are considered to be key regulators of the progression of a variety of human cancers,including gastric cancer.Studies have shown that circRASSF2 acts as an oncogene to regulate cancer progression.However,its role and underlying molecular mechanisms in gastric cancer progression are still unclear.AIM To explore the molecular mechanism by which circRASSF2 regulates gastric cancer cell proliferation,migration,and apoptosis.METHODS The expression of circRASSF2 and miR-218-5p in gastric cancer tissues,adjacent tissues,and GES-1,HGC-27 and AGS cells was examined by real-time quantitative PCR.Dual luciferase reporter assay was used to assess the targeting relationship of circRASSF2 and miR-218-5p.HGC-27 and AGS cells were divided into the following groups:si-circRASSF2 group,si-NC group,miR-218-5p mimic group,miR-NC group,si-circRASSF2+anti-miR-NC group,and si-circRASSF2+miR-218-5p inhibitor group.MTT assay and clone formation assay were used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.Transwell assay was used to detect cell migration.RESULTS CircRASSF2 expression increased and miR-218-5p expression decreased in gastric cancer tissues,and their expression was negatively correlated(P<0.05);circRASSF2 was upregulated and miR-218-5p was downregulated in gastric cancer HGC-27 and AGS cells(P<0.05).Dual luciferase reporter assay showed that circRASSF2 targets miR-218-5p.CircRASSF2 knockdown or miR-218-5p overexpression increased HGC-27 and AGS cell poptosis,while reduced cell proliferation and migration(P<0.05).Down-regulation of miR-218-5p reversed the effect of circRASSF2 knockdown on cell proliferation,migration,and apoptosis.CONCLUSION CircRASSF2 promotes proliferation and migration and suppresses apoptosis of gastric cancer cells by targeting miR-218-5p.
关 键 词:circRASSF2 miR-218-5p 胃癌 增殖 迁移 凋亡 基因表达调控
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