miR-495 andmiR-5688 are down-regulated in non-small cell lung cancer under hypoxia to maintain interleukin-11 expression  

作　　者：Meng Zhao Jiao Chang Ran Liu Yahui Liu Jin Qi Yanhui Wang Xinwei Zhang Lu Qiao Yu Jin Haohua An Li Ren 

机构地区：[1]Department of Clinical Laboratory,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Cancer,National Human Genetic Resources Sharing Service Platform,Tianjin 300060,P.R.China [2]Department of Immunology,Tianjin Key Laboratory of Cellular and Molecular Immunology,Key Laboratory of Educational Ministry of China,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,P.R.China [3]Department of Radiology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Cancer,National Human Genetic Resources Sharing Service Platform,Tianjin 300060,P.R.China

出　　处：《Cancer Communications》2020年第9期435-452,共18页癌症通讯（英文）

基　　金：supported by the National Natural Science Foundation of China(No.81602026);the Natural Science Foundation of Tianjin(No.18JCQNJC81600 and 18JCZDJC32600).

摘　　要：Background:Hypoxia is a hallmark of cancer and is associated with poor prognosis.However,the molecular mechanism by which hypoxia promotes tumor progression remains unclear.MicroRNAs dysregulation has been shown to play a critical role in the tumor and tumor microenvironment.Here,we investigated the roles ofmiR-495 and miR-5688 in human non-small cell lung cancer(NSCLC)and their underlying mechanism.Methods:The expression levels of miR-495 and miR-5688 in human NSCLC tissue specimens were measured by quantitative real-time polymerase chain reaction(qRT-PCR).Deferoxamine(DFO)was used to determine whether the regulation of miR-495 and miR-5688 under hypoxia was dependent on hypoxia-inducible factor 1-alpha(HIF-1α).Furthermore,the functions of miR-495 and miR-5688 in tumor progression were evaluated using colony formation,3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium(MTS),wound healing,transwell assays,and xenograft model.Two algorithms,PicTAR and Targetscan,were used to predict the target gene of these two miRNAs,and dual-luciferase reporter assay was conducted to confirm the target.The unpaired two-tailed t test,Pearson correlation analysis,and Fisher’s exact probability test were performed for statistical analyses.Results:Two miRNAs,miR-495 and miR-5688,were found to participate in NSCLC progression under hypoxia.They were down-regulated in NSCLC tissues compared with normal tissues.We determined that hypoxia led to the down-regulation of miR-495 and miR-5688 in NSCLC cells,which was independent of HIF-1αand cellular metabolic energy.In addition,miR-495 and miR-5688 suppressed cell proliferation,migration,and invasion in vitro.The NSCLC xenograft model showed that miR-495 and miR-5688 inhibited tumor formation in vivo.Interestingly,we found that miR-495 and miR-5688 had the same target,interleukin-11(IL-11).Recombinant human IL-11 counteracted the effects of miR-495 and miR-5688 on NSCLC cells,suggesting that miR-495 and miR-5688 executed their tumor suppressive role

关 键 词：HYPOXIA INTERLEUKIN-11 miR-495 miR-5688 non-small cell lung cancer PicTAR Targetscan 

分 类 号：R73[医药卫生—肿瘤]