miR-375靶向调控JAK2表达抑制胃癌细胞增殖、侵袭与迁移

Targeted regulation of JAK2 expression by miR-375 and its inhibition on proliferation,invasion and migration of gastric cancer cells

目的:研究miR-375对胃癌细胞增殖、迁移与侵袭的影响,以及可能的调控机制。方法:实时荧光定量PCR检测胃癌组织、癌旁组织和3种胃癌细胞系(MKN28、SGC-7901和BGC-823)中miR-375的表达水平;双荧光素酶报告基因检测miR-375与JAK2的靶向作用关系;Western blot检测SGC-7901细胞中JAK2蛋白的表达情况;MTT检测miR-375对SGC-7901细胞增殖能力的影响;Transwell小室法检测miR-375对SGC-7901细胞侵袭与迁移能力的影响。结果:实时荧光定量qPCR结果显示,miR-375在胃癌组织中的表达量明显低于癌旁组织(P<0.05),JAK2在胃癌组织中的表达量高于癌旁组织(P<0.05);3种胃癌细胞株中,SGC-7901细胞中miR-375表达量最低;miR-375与JAK23’-UTR有特异性结合区域,miR-375靶向调控JAK2的表达;转染miR-375模拟物后,SGC-7901细胞的增殖、侵袭与迁移的能力显著减弱(P<0.05)。结论:miR-375在胃癌的发生发展过程中起重要作用,可以通过靶向调控JAK2来抑制胃癌SGC-7901细胞的恶性生物学行为。

Objective:To study the effects of miR-375 on the proliferation,migration and invasion of gastric cancer cells,and the possible regulatory mechanisms.Methods:Fluorescence quantitative PCR to detect the expression level of miR-375 in gastric cancer tissues,adjacent tissues and three gastric cancer cell lines(MKN28,SGC-7901 and BGC-823);dual luciferase reporter gene to detect the targeting of miR-375 and JAK2 Function relationship;Western blot to detect the expression of JAK2 protein in SGC-7901 cells;MTT to detect the effect of miR-375 on the proliferation ability of SGC-7901 cells;Transwell chamber method to detect the effect of miR-375 on the invasion and migration ability of SGC-7901 cells.Results:qPCR results showed that the expression level of miR-375 in gastric cancer tissues was significantly lower than that in adjacent tissues(P<0.05),the expression of JAK2 in gastric cancer tissues was higher than that in adjacent tissues(P<0.05);3 gastric cancer cell lines In SGC-7901 cells,the expression level of miR-375 was the lowest;miR-375 and JAK23'UTR had specific binding regions,miR-375 targeted to regulate JAK2 expression;transfected miR-375 mimics After that,the ability of SGC-7901 cells to proliferate,invade and migrate significantly decreased(P<0.05).Conclusion:miR-375 plays an important role in the occurrence and development of gastric cancer.It can inhibit the malignant biological behavior of gastric cancer SGC-7901 cells by targeting JAK2.