miR-216a-5p调控HMGB1参与膀胱癌EJ细胞生物学行为的机制探讨

Mechanism of miR-216a-5p regulating HMGB1 participates in the biological behavior of bladder cancer EJ cells

[目的]探究微小RNA(microRNA,miR)-216a-5p靶向高迁移率族蛋白1(HMGB1)调控膀胱癌细胞的增殖、凋亡和侵袭的机制。[方法]通过双荧光素酶报告验证miR-216a-5p与HMGB1的靶向关系。人膀胱癌细胞分为4组:对照组、miR-216a-5p组、HMGB1组和miR-216a-5p+HMGB1组。通过转染miR-216a-5p类似物和/或HMGB1质粒来提高miR-216a-5p和/或HMGB1的水平。检测各组miR-216a-5p和HMGB1蛋白表达水平,以及细胞增殖、凋亡和侵袭能力。[结果] miR-216a-5p与HMGB1在膀胱癌细胞中的靶向结合(P<0.05)。HMGB1蛋白及其细胞的增殖及侵袭水平在miR-216a-5p组中明显较对照组低,凋亡率显著高于对照组(P<0.05)。HMGB1组的HMGB1蛋白、增殖和侵袭水平显著高于对照组,凋亡率显著低于对照组(P<0.05)。miR-216a-5p+HMGB1组的HMGB1蛋白、增殖和侵袭水平显著高于miR-216a-5p组且显著低于HMGB1组,凋亡率显著低于miR-216a-5p组且显著高于HMGB1组(P<0.05)。[结论]miR-216a-5p可利用靶向抑制HMGB1蛋白分泌发挥将膀胱癌的细胞侵袭和增殖和抑制,并加速细胞的凋亡,可能成为膀胱癌潜在的治疗靶点。

[Objective]To explore the mechanism by which microRNA(miR)-216a-5p targets high mobility group protein box 1(HMGB1) to regulate the proliferation, apoptosis and invasion of bladder cancer cells.[Method]The target relationship between miR-216a-5p and HMGB1 was verified by dual luciferase report.Human bladder cancer cells were divided into 4 groups: control group, miR-216a-5p group, HMGB1 group and miR-216a-5p+HMGB1 group.The level of miR-216a-5p and/or HMGB1 were increased by transfection of miR-216a-5p mimic and/or HMGB1 plasmid.The expression levels of miR-216a-5p and HMGB1 protein in each group, as well as the cell proliferation, apoptosis and invasion abilities were detected.[Result]miR-216a-5p targeted binding HMGB1 in bladder cancer cells(P<0.05).The levels of HMGB1 protein, proliferation and invasion of miR-216a-5p group were obvious lower than control group, and the apoptosis rate(18.46±1.54%) was obvious higher than control group(P<0.05).The HMGB1 protein, proliferation and invasion levels of the HMGB1 group were obvious higher than control group, and the apoptosis rate was obvious lower than control group(P<0.05).The level of HMGB1 protein, proliferation and invasion of miR-216a-5p+HMGB1 group were obvious higher than miR-216a-5p group and obvious lower HMGB1 group, and the apoptotic rate was obvious lower than miR-216a-5p group and obvious higher than HMGB1 group(P<0.05).[Conclusion]miR-216a-5p can inhibit the proliferation and invasion of bladder cancer cells by targeting the expression of HMGB1 protein, and promote apoptosis, which may be a potential therapeutic target for bladder cancer.