miR-21、miR-182、miR-382在非小细胞肺癌中的临床意义及益气除痰法的干预作用  

Clinical Significance of miR-21,miR-182 and miR-382 in Non-Small Cell Lung Cancer and Intervention Effect of Qi-Replenishing and Phlegm-Removing Therapy

作　　者：孙玲玲[1] 乔靖[1] 伍家鸣 林丽珠[1] SUN Ling-Ling;QIAO Jing;WU Jia-Ming;LIN Li-Zhu(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405

出　　处：《广州中医药大学学报》2021年第3期548-555,共8页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(编号:81973775,81573780);广东省自然科学基金资助项目(编号:2020A1515011176)。

摘　　要：【目的】分析miR-21、miR-182、miR-382基因对肺癌进展的影响及益气除痰法的干预作用。【方法】应用生存分析在线软件Kaplan-Meier plotter分析miR-21、miR-182、miR-382对肺癌预后的影响,应用功能富集分析工具FunRich数据库对miR-21、miR-182、miR-382进行功能富集、通路富集分析,GeneMANIA数据库分析靶基因蛋白的互作网络。选取单纯中药治疗中晚期非小细胞肺癌患者(设为“中医组”)和中药联合维持化疗的中晚期非小细胞肺癌患者(设为“结合组”),采用定量聚合酶链反应(PCR)方法分析益气除痰法对患者外周血中miR-21、miR-182、miR-382表达的影响。【结果】miR-21、miR-382的表达量与肺腺癌的生存期呈负相关,与肺鳞癌的生存期关系不明显。miR-182的表达量与肺腺癌患者的生存期无明显相关性,与肺鳞癌的生存期呈正相关。miR-21、miR-182、miR-382靶基因的功能主要为信号传导、细胞之间的通讯,所涉及的信号通路主要包括:整合素家族信号通路、血管内皮生长因子(VEGF)/血管内皮生长因子受体(VEGFR)通路及肿瘤坏死因子相关凋亡诱导配体(TRAIL)通路等。miR-21与肿瘤转移密切相关的靶基因包括:RECK、TNFRSF11B、TGFBI、PDCD4、SPRY2、FOXF2。中医组miR-21的增加水平较结合组低。【结论】miR-21可能影响肿瘤转移及肺腺癌的生存,益气除痰法可能通过调控miR-21的表达有效治疗中晚期非小细胞肺癌。Objective To analyze the effects of miR-21,miR-182,miR-382 genes on the progression of lung cancer and the intervention effect of qi-replenishing and phlegm-removing therapy.Methods The effects of miR-21,miR-182 and miR-382 on prognosis of lung cancer were analyzed by online software Kaplan-Meier plotter,the functional enrichment and pathway enrichment of miR-21,miR-182 and miR-382 were analyzed by FunRich database,and the interaction network of target gene proteins was analyzed by GeneMANIA database.We selected the non-small-cell lung cancer(NSCLC)patients received Chinese herbal medicine alone(served as Chinese medicine group)and the NSCLC patients received Chinese herbal medicine combined with chemotherapy(served as combination group),Quantitative polymerase chain reaction(PCR)was used to analyze the effect of qireplenishing and phlegm-removing therapy on the expression of miR-21,miR-182 and miR-382 in peripheral blood of the patients.Results The expression level of miR-21 and miR-382 was negatively correlated with the survival period of lung adenocarcinoma,but had no obvious correlation with the survival period of lung squamous cell carcinoma.The expression level of miR-182 had no significant correlation with the survival period of lung adenocarcinoma,but was positively correlated with survival of patients with lung squamous cell carcinoma.The functions of target genes of miR-21,miR-182,miR-382 were mainly related to signal transduction and intercellular communication,and the involved signal pathways mainly included integrin family signal pathway,vascular endothelial growth factor(VEGF)/vascular endothelial growth factor receptor(VEGFR)pathway,necrosis factor-related apoptosis-inducing ligand(TRAIL)pathway.The miR-21 target genes such as RECK,TNFRSF11B,TGFBI,PDCD4,SPRY2,FOXF2 was associated with tumor metastasis.The increase level of miR-21 in the Chinese medicine group was lower than that in the combination group.Conclusion miR-21 has possible effects on tumor metastasis and survival of lung adenocarcinoma.Q

关 键 词：益气除痰法 肺癌 MIR-21 miR-182 miR-382 生存 

分 类 号：R285.5[医药卫生—中药学]