IL-8/miR-182正反馈调控轴在非小细胞肺癌中的作用机制研究  

Mechanism of IL-8/miR-182 positive feedback regulatory axis in non-small cell lung cancer

作　　者：赵明娜 张宸梓 洪秋双 娄加陶[1] ZHAO Mingna;ZHANG Chenzi;HONG Qiushuang;LOU Jiatao(Clinical Laboratory Medicine Center,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China;Department of Hematology,Xiangya Hospital,Central South University,Changsha 410008,Hunan,China;Clinical Laboratory Medicine Center,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海交通大学医学院附属第一人民医院检验医学中心,上海200080 [2]中南大学湘雅医院血液科,湖南长沙410008 [3]上海中医药大学附属岳阳中西医结合医院检验实验医学中心,上海200437

出　　处：《检验医学》2022年第4期349-355,共7页Laboratory Medicine

基　　金：上海市自然科学基金资助项目(22ZR1450200)。

摘　　要：目的探讨白细胞介素-8(IL-8)和微小RNA-182(miR-182)在非小细胞肺癌(NSCLC)中的相互作用,及促进NSCLC细胞增殖和侵袭的机制。方法选取NSCLC患者40例(NSCLC组),收集其术前血清样本和术中切除的癌组织及癌旁组织样本。以40名体检健康者作为正常对照组。检测血清IL-8水平和癌组织、癌旁组织miR-182表达量。采用细胞学相关实验分析miR-182和IL-8对人NSCLC细胞株A549增殖和侵袭的影响、IL-8对miR-182的调节作用,以及miR-182影响IL-8表达的信号通路。结果NSCLC组血清IL-8水平显著高于正常对照组(P<0.01)。NSCLC患者癌组织miR-182相对表达量显著高于癌旁组织(P<0.01)。IL-8通过miR-182促进A549细胞的增殖和侵袭。IL-8通过信号转导及转录激活因子3(STAT3)上调miR-182的表达。miR-182通过调节NF-κB信号通路上调IL-8的表达。结论NSCLC患者IL-8和miR-182均呈高表达,且通过IL-8/STAT3/miR-182/NF-κB/IL-8正反馈调控轴促进NSCLC的发生、发展。Objective To investigate the interaction between interleukin-8(IL-8)and microRNA-182(miR-182)in non-small cell lung cancer(NSCLC)and the mechanism of promoting the proliferation and migration of NSCLC.Methods A total of 40 patients with NSCLC(NSCLC group)were enrolled to collect preoperative serum samples and intraoperative cancer tissues and adjacent tissues.Another 40 healthy subjects(healthy control group)were enrolled as well.Serum IL-8 level and the expression level of miR-182 in cancer and adjacent tissues were determined.Cytological experiments were performed to analyze the effects of miR-182 and IL-8 on proliferation and migration of human NSCLC cell line A549,the regulatory effect of IL-8 on miR-182 and the signaling pathway of miR-182 affecting IL-8 expression.Results Serum IL-8 level in NSCLC group was higher than that in healthy control group(P<0.01).The relative expression of miR-182 in cancer tissues of NSCLC patients was higher than that in adjacent tissues(P<0.01).IL-8 promoted the proliferation and migration of A549 cells through miR-182.IL-8 up-regulated the expression of miR-182 through signal transducer and activator of transcription 3(STAT3).MiR-182 up-regulated IL-8 expression by regulating nuclear factor-κB(NF-κB)signaling pathway.Conclusions Both IL-8 and miR-182 are highly expressed in NSCLC patients,and the positive feedback regulatory axis of IL-8/STAT3/miR-182/NF-κB/IL-8 promotes the occurrence and development of NSCLC.

关 键 词：白细胞介素-8 微小RNA-182 增殖 侵袭 非小细胞肺癌 

分 类 号：R446.62[医药卫生—诊断学]