GK-IT1抑制JAK信号通路对胃癌细胞增殖和侵袭迁移的影响  

Effects of GK-IT1 on proliferation,migration and invasion of gastric cancer cells via JAK signaling pathway

作　　者：王琼[1] 李辉 伍勇彬 WANG Qiong;LI Hui;WU Yongbin(Department of Gastroenterology,Ziyang First People′s Hospital,Ziyang 641300,China)

机构地区：[1]资阳市第一人民医院消化内科,四川资阳641300 [2]资阳市第一人民医院肿瘤中心,641300

出　　处：《临床肿瘤学杂志》2023年第12期974-979,共6页Chinese Clinical Oncology

摘　　要：目的研究长链非编码RNA GK内含子转录本1(GK-IT1)通过Janus激酶(JAK)信号通路对胃癌细胞生物学活性的影响。方法UALCAN平台分析胃癌组织中GK-IT1的表达。通过实时定量PCR(qPCR)评估GK-IT1在人胃癌细胞中的表达。BSG-823细胞进行GK-IT1干扰片段si-GK-IT转染或si-GK-IT转染与JAK2信号通路激活剂Coumermycin A1两者联合处理,分为阴性对照组、si-GK-IT1组和si-GK-IT1+JAK2组。通过CCK-8、划痕和Transwell实验评估细胞增殖、迁移和侵袭情况。qPCR或Western blot检测B细胞淋巴瘤2(Bcl-2)、裂解的半胱氨酸天冬氨酸蛋白酶3(CCP3)、基质金属蛋白酶9(MMP-9)和磷酸化Janus激酶2(p-JAK2)的表达。结果GK-IT1在胃癌组织中表达上调,且与肿瘤分期和分级有关(P<0.05)。与胃黏膜上皮细胞RGM-1相比,胃癌细胞中GK-IT1表达水平更高(P<0.05)。与阴性对照组相比,si-GK-IT1组细胞增殖、迁移和侵袭能力减弱;si-GK-IT1+JAK2组逆转了上述结果(P<0.05)。与阴性对照组相比,si-GK-IT1组Bcl-2、MMP-9和p-JAK2的表达降低,而CCP3的表达升高(P<0.05);与si-GK-IT1组相比,除CCP3表达降低外,si-GK-IT1+JAK2组的其余因子表达增加(P<0.05)。结论GK-IT1通过JAK信号通路抑制来调控胃癌细胞的增殖和迁移侵袭过程,有望成为胃癌的潜在靶点。Objective To examine the effects of long non-coding RNA GK intronic transcript 1(GK-IT1)on the biological activities of gastric cancer cells via the Janus kinase(JAK)signaling pathway.Methods UALCAN was applied to analyze the expression of GK-IT1 in gastric cancer tissues.Expressions of GK-IT1 in human gastric cancer cell lines were evaluated by quantitative real-time polymerase chain reaction(qPCR)assay.BSG-823 cells were treated with small interference RNA(siRNA)against GK-IT1 si-GK-IT1,or si-GK-IT1 and Coumermycin A1(an activator of the JAK2 signaling pathway)both in combination,and allocated into Negative control group,si-GK-IT1 group and si-GK-IT1+JAK2 group.Cell proliferation,migration and invasion were evaluated by CCK-8,scratch and Transwell assays.Expressions of B-cell lymphoma-2(Bcl-2),cleaved-caspase-3(CCP3),matrix metallopeptidase-9(MMP-9)and phosphorylated Janus-activated kinase 2(p-JAK2)were tested by qPCR or Western blot assays.Results GK-IT1 was upregulated in gastric cancer tissues and related with tumor stage and grade(P<0.05).Gastric cancer cells showed higher expression of GK-IT1 compared to the findings in gastric mucosal epithelial RGM-1 cell(P<0.05).Moreover,si-GKIT1 group exhibited blunted abilities of proliferation,migration and invasion compared to Negative control group(P<0.05),whereas si-GK-IT1+JAK2 group reversed these results(P<0.05).Compared with the Negative control group,the expression of Bcl-2,MMP-9 and p-JAK2 in the si-GK-IT1 group decreased,while expression of CCP3 in the si-GK-IT1 group increased(P<0.05).Compared with the si-GK-IT1 group,in addition to the decreased expression of CCP3,the si-GK-IT1+JAK2 group showed an increase in the expression of the rest factors(P<0.05).Conclusion GK-IT1 regulates the proliferation,migration,and invasion of gastric cancer cells through inhibition of the JAK signaling pathway,and is expected to become a potential target for gastric cancer treatment.

关 键 词：胃癌 GK内含子转录本1 增殖 侵袭迁移 JAK信号通路 

分 类 号：R735.2[医药卫生—肿瘤]