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Common mechanism of Citrus Grandis Exocarpium in treatment of chronic obstructive pulmonary disease and lung cancer

Chinese Herbal Medicines 2021年第4期13卷 525-533页

作者： Wei Zhou Min Dong Hao Wu Hui-lin Li Jia-le Xie Ru-yun Ma Wei-wei Su Jian-ye Dai School of Pharmacy Lanzhou UniversityLanzhou 730000China Department of Pulmonology Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730000China guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-marketed TCM Guangdong Key Laboratory of Plant ResourcesSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China

Objective:"Same treatment for different diseases"is a unique treatment strategy in traditional Chinese *** kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease(COPD)and lung *** Grandis Exocarpium(Huajuhong in Chinese,HJH),a famous herbal,is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on"syndrome differentiation and treatment"***,the common mechanism for HJH’s treatment of COPD and lung cancer is not ***:In this study,based on network pharmacology and molecular docking technology,the common mechanism of HJH in the treatment of COPD and lung cancer was *** active ingredients and related targets of HJH were integrated from TCMSP,BATMAN-TAM,STP,and Pubchem *** standard names of these targets were united by Uni Prot *** of COPD and lung cancer were enriched through Gene Cards,NCBI(Gene),Therapeutic target Database,and Dis Ge NET(v7.0)*** the intersection targets of HJH and diseases were *** STRING network and the Cytoscape 3.7.2 were used to construct PPI network,the DAVID database was used to perform GO and KEGG *** Cytoscape 3.6.1 was used to build"ingredient-target-signal pathway"***,Auto Dock 1.5.6 software was used to perform molecular docking of key proteins and ***:Eleven active ingredients in HJH were obtained by searching the database,corresponding to 184 HJH-COPD-lung cancer targets *** results of biological network analysis showed that naringenin,the active component in HJH,could mainly act on target proteins such as AKT1,*** through positive regulation of vasoconstriction and other biological processes,naringenin could regulate estrogen signaling pathway,VEGF signaling pathway,HIF-1 signaling pathway,Erb B signaling pathway,PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung can

关键词： chronic obstructive pulmonary disease Citrus Grandis Exocarpium lung cancer mechanism molecular docking network pharmacology same treatment for different diseases

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CMKLR1 senses chemerin/resolvin E1 to control adipose thermogenesis and modulate metabolic homeostasis

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Fundamental Research 2024年第3期4卷 575-588页

作者： Zewei Zhao Siqi Liu Bingxiu Qian Lin Zhou Jianglin Shi Junxi Liu Lin Xu Zhonghan Yang Department of Biochemistry Molecular Cancer Research CenterSchool of MedicineSun Yat-sen UniversityShenzhenGuangdong 518107China Department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Public Health Sun Yat-sen UniversityGuangzhouGuangdong 510080China

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in ***,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical *** study aimed at identifying a potential GPCR target to induce beige *** found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat ***,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat ***,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling *** further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of *** conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

关键词： Obesity Insulin resistance Thermogenesis CMKLR1 Resolvin E1 Chemerin

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Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression

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Chinese Journal of Cancer Research 2023年第2期35卷 140-162页

作者： Qian Guan Huiran Lin Wenfeng Hua Lei Lin Jiabin Liu Linqing Deng Jiao Zhang Jiwen Cheng Zhonghua Yang Yong Li Jun Bian Haixia Zhou Suhong Li Li Li Lei Miao Huimin Xia Jing He Zhenjian Zhuo School of Medicine South China University of TechnologyGuangzhou 510006China Department of Pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangdong Provincial Clinical Research Center for Child HealthGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Faculty of Medicine Macao University of Science and TechnologyMacao 99078China Research Institute for Maternal and Child Health Guangdong Second Provincial General HospitalGuangzhou 510317China Department of Pediatric Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Pediatric Surgery the Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004China Department of Pediatric Surgery Shengjing Hospital of China Medical UniversityShenyang 110004China Department of Pediatric Surgery Hunan Children's HospitalChangsha 410004China Department of General Surgery Xi'an Children's HospitalXi'an Jiaotong University Affliated Children's HospitalXi'an 710003China Department of Hematology The Second Affliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhou 325027China Department of Pathology Children Hospital and Women Health Center of ShanxiTaiyuan 030013China Kunming key laboratory of Children Infection and Immunity Yunnan Key Laboratory of Children's Major Disease ResearchYunnan Institute of Pediatrics ResearchYunnan Medical Center for Pediatric DiseasesKunming Children's HospitalKunming 650228China laboratory Animal Center School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhen 518055China

Objective:AlkB homolog 5(ALKBH5)has been proven to be closely related to ***,the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been ***:The potential functional single-nucleotide polymorphisms(SNPs)in ALKBH5 were identified by National Center for Biotechnology Information(NCBI)dbSNP screening and SNPinfo *** probes were used for genotyping.A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of *** expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry(IHC).Cell counting kit-8(CCK-8),plate colony formation and 5-ethynyl-2'-deoxyuridine(EdU)incorporation assays were used to evaluate cell *** healing and Transwell assays were used to compare cell migration and *** modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A *** sequencing,N6-methyladenosine(mA)sequencing,mA methylated RNA immunoprecipitation(MeRIP)and a luciferase assay were used to identify the targeting effect of ALKBH5 on ***:ALKBH5 was highly expressed in *** down ALKBH5 inhibited the proliferation,migration and invasion of cancer ***-186-3p negatively regulates the expression of ALKBH5,and this ability is affected by the rs8400 *** the G nucleotide was mutated to A,the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased,resulting in upregulation of *** is the downstream target gene of the ALKBH5 *** down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on *** of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in ***:We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanism

关键词： Neuroblastoma risk ALKBH5 polymorphism progression

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Kinectin 1 promotes the growth of triple-negative breast cancer via directly co-activating NF-kappaB/p65 and enhancing its transcriptional activity

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Signal Transduction and targeted Therapy 2021年第8期6卷 2472-2483页

作者： Lin Gao Shanze Chen Malin Hong Wenbin Zhou Bilan Wang Junying Qiu Jinquan Xia Pan Zhao Li Fu Jigang Wang Yong Dai Ni Xie Qinhe Yang Hsien-Da Huang Xiang Gao Chang Zou Department of Clinical Medical Research Center The Second Clinical Medical CollegeJinan University(Shenzhen Peopled Hospital)The First Affiliated Hospital of Southern University of Science and TechnologyShenzhenGuangdongPR China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhouGuangdongPR China Department of Respiratory and Critical Care Medicine First Affiliated Hospital of Southern University of Science and TechnologyThe Second Clinical Medical CollegeJinan University(Shenzhen Peopled Hospital)Shenzhen Institute of Respiratory DiseasesShenzhenGuangdongPR China Shenzhen Public Service Platform on Tumor Precision Medicine and molecular Diagnosis the Second Clinical Medical CollegeJinan University(Shenzhen People's Hospital)ShenzhenGuangdongPR China Department of Pharmacy West China Second University Hospital of Sichuan UniversityChengduPR China guangdong provincial key laboratory of Regional Immunity and Diseases Department of Pharmacology and International Cancer CenterShenzhen University Health Science CenterShenzhenGuangdongChina Department of Integrated Chinese and Western Medicine Jinan UniversityGuangzhouGuangdongPR China School of Life and Health Sciences The Chinese University of Kong HongShenzhenChina Warshel Institute for Computational Biology The Chinese University of HongKongShenzhenChina Department of Neurosurgery State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduPR China

Triple-negative breast cancer(TNBC)is the most challenging subtype of breast *** endeavor has been made to explore the molecular biology basis of ***,we reported a novel function of factor Kinectin 1(KTN1)as a carcinogenic promoter in ***1 expression in TNBC was increased compared with adjacent tissues or luminal or Her2 subtypes of breast cancer,and TNBC patients with high KTN1 expression have poor *** functional studies,knockdown of KTN1 inhibited the proliferation and invasiveness of TNBC both in vitro and in vivo,while overexpression of KTN1 promoted cancer cell proliferation and ***-seq analysis revealed that the interaction of cytokine-cytokine receptor,particularly CXCL8 gene,was upregulated by KTN1,which was supported by the further ***8 depletion inhibited the tumorigenesis and progression of ***,rescue experiments validated that KTN1-mediated cell growth acceleration in TNBC was dependent on CXCL8 both in vitro and in ***,it was found that KTN1 enhanced the phosphorylation of NF-κB/p65 protein at Ser536 site,and specifically bound to NF-κB/p65 protein in the nucleus and cytoplasm of ***,the transcription of CXCL8 gene was directly upregulated by the complex of KTN1 and NF-κB/p65 *** together,our results elucidated a novel mechanism of KTN1 gene in TNBC tumorigenesis and ***1 may be a potential molecular target for the development of TNBC treatment.

关键词： inhibited breast cancer

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Dehydrocostus lactone exerts the antitumor effect in non-small cell lung cancer H1299 cells

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TMR Cancer 2020年第3期3卷 101-111页

作者： Chao-Yue Su Hui Wang Yan-Rui Pan Ling-Ling Zhang Qiao-Ru Guo Yan-Yan Yan Jia-Jun Li Jia-Li Fu Xin-YueFan Yu-Qing Wang Jian-Ye Zhang guangdong provincial key laboratory of molecular target&Clinical Pharmacology School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436 China.2guangzhou Institute of Pediatrics/guangzhou Women and Children’s Medical Center Guangzhou Medical UniversityGuangzhou 510623 China.3Institute of Respiratory and Occupational Diseases Collaborative Innovation Center for CancerMedical CollegeShanxi Datong UniversityDatong 037009 China.4key laboratory of Tropical Translational Medicine of Ministry of Education Hainan Medical UniversityHaikou571199P.R.China

Background:Dehydrocostus lactone(DHC),a sesquiterpene lactone derived from Aucklandiae Radix,has been proved to possess various pharmacological ***,studies have reported that DHC has potential antitumor ***,few studies have reported the effect of DHC on non-small cell lung cancer(NSCLC).Here,we investigated the antitumor effect of DHC in NSCLC H1299 ***:MTT assay and colony formation assay was used to assess the anti-proliferation effects of DHC in H1299 *** healing and Transwell assays were utilized to determine the inhibitory effects of migration and invasion,*** was detected using the Annexin V/propidium iodide ***-time-quantitative PCR(RT-qPCR)was used to detect the mRNA expression ***:We demonstrated here that DHC inhibited the proliferation,migration and invasion of H1299 cells in a dose-or time-dependent ***,after treating with DHC at the concentration of 32.0μM,the apoptosis of H1299 cells was significantly ***,DHC affected the mRNA expression of E-cadherin,N-cadherin,Snail,c-Myc,integrinα2,Survivin and matrix metalloproteinase ***:To summarize,our data support that DHC can inhibit proliferation,invasion,migration and induced apoptosis of NSCLC H1299 *** should be considered for its potential for adjuvant therapeutic development.

关键词： Dehydrocostus lactone Non-small cell lung cancer Apoptosis Migration Invasion

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CircMYBL2 facilitates hepatocellular carcinoma progression by regulating E2F1 expression

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Oncology Research 2024年第6期32卷 1129-1139页

作者： JUNZHE YI BINBIN LI XIAOMIN YIN LINGRUI LIU CAILU SONG YING ZHAO MANBO CAI HAILIN TANG DONG CHEN NING LYU State key laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of Medical Oncology The Third People’s Hospital of YongzhouYongzhou425000China Department of Radiotherapy The First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyang421001China Center of Hepato-Pancreato-Biliary Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China

Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain *** sought to unveil the expression profile and biological role of circMYBL2 in *** microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of *** experiments were conducted to evaluate the biological function of circMYBL2 in HCC ***,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and ***2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell *** expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting ***,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging *** findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.

关键词： Circular RNAs circMYBL2 miR-1205 E2F1 Hepatocellular carcinoma

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Ribosome biogenesis in disease:new players and therapeutic targets

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Signal Transduction and targeted Therapy 2023年第2期8卷 484-505页

作者： Lijuan Jiao Yuzhe Liu Xi-Yong Yu Xiangbin Pan Yu Zhang Junchu Tu Yao-Hua Song Yangxin Li Institute for Cardiovascular Science and Department of Cardiovascular Surgery First Affiliated Hospital and Medical College of Soochow UniversityCollaborative Innovation Center of HematologySoochow UniversitySuzhouJiangsu215123P.R.China Department of Orthopedics the Second Hospital of Jilin UniversityChangchunJilin130000P.R.China key laboratory of molecular target&Clinical Pharmacology and the NMPA State key laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhouGuangdong511436P.R.China Department of Structural Heart Disease National Center for Cardiovascular DiseaseChina&Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingP.R.China key laboratory of Cardiovascular Appratus Innovation Beijing100037P.R.China Cyrus Tang Hematology Center Collaborative Innovation Center of HematologySoochow UniversityNational Clinical Research Center for Hematologic Diseasesthe First Affiliated Hospital of Soochow UniversitySuzhouP.R.China State key laboratory of Radiation Medicine and Protection Soochow UniversitySuzhou215123P.R.China

The ribosome is a multi-unit complex that translates mRNA into *** biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,development,and *** mTORC1,Myc,and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein *** of mTORC1 is required for normal fetal growth and development and tissue regeneration after *** is implicated in cancer development by enhancing RNA Pol II activity,leading to uncontrolled cancer cell *** deregulation of noncoding RNAs such as microRNAs,long noncoding RNAs,and circular RNAs is involved in developing blood,neurodegenerative diseases,and *** review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial *** also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting,ribosome-stalling,and *** summarize the role of ribosome biogenesis in the development of various ***,we review the current clinical trials,prospective vaccines for COVID-19,and therapies targeting ribosome biogenesis in cancer,cardiovascular disease,aging,and neurodegenerative disease.

关键词： mTORC1 consequences jointly

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Integration of scRNA-Seq and Bulk RNA-Seq to analyze the heterogeneity ofcolorectal cancer immune cells and establish a molecular risk model

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Cancer Advances 2023年第22期6卷 1-10页

作者： Li-Yue Sun Jiao-Jiao Yang Xin-Xin Zeng Yu-Ying Jiang Ju Shen Fang Wang Xu-Hui Zhang second Department of Oncology The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhouGuangdong Province 510317China Department of molecular Diagnostics Sun Yat-sen University Cancer CenterGuangzhouGuangdong Province 510317China guangdong Medical University ZhanjiangGuangdong Province 524000China

Background:Colorectal cancer(CRC)is a highly heterogeneous malignant tumor that significantly impacts clinical diagnosis and ***-cell RNA sequencing is an innovative method for exploring tumor heterogeneity and understanding its role at cellular and genetic ***:The colorectal cancer Single-cell RNA sequencing data were analysed on the ***-seq data in bulk form was utilized to assess the major genes of the immune cell subsets linked to *** conducted an analysis of the abundance of immune cells in the microenvironment of CRC,and also performed weighted gene co-expression network *** set enrichment analysis helped perform two analytical procedures of subtype ***,Least absolute shrinkage and selection operator regression was employed to analyse and screen for a gene ***,quantitative PCR Was performed to detect the expression levels of signature genes in ***:The Single-cell RNA sequencing(GSE146771)dataset was integrated to obtain 9 cell *** Single-sample gene set enrichment analysis showed that the related gene expression of T-cell subsets of different functional statuses could vary greatly between patients with *** cell analysis of TCGA-CRC indicated an improved overall survival rate for patients with elevated Th2 cell ***-gene signature(Risk Score=-0.205×CDC25C-0.231×GSTCD-0.010×KPNA2-0.002×KIF15-0.171×ORC1)was developed by weighted correlation network analysis,and lasso Cox ***,the risk prediction efficacy of the signature was validated in four GSE ***,the expression of five genes was reduced in CRC tissue by quantitative ***:Five-gene signature based on CRC heterogeneity was developed as a prognosis predictor,which can serve as a potential treatment target.

关键词： colorectal cancer scRNA-seq Th2 cells 5-gene signature risk prognosis

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Basing on microRNA-mRNA analysis identifies microRNA in exosomes associated with wound repair of diabetic ulcers

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BIOCELL 2021年第1期45卷 27-39页

作者： PENG LIU ANFANG ZOU QI CHEN BIAO CHENG QIN LI Department of Burn&Plastic Surgery General Hospital of Southern Theatre Command of PLAGuangzhou510010China Huabo Post-Doctoral Research Center Biological Pharmaceutical Research InstituteGuangzhou510515China Department of Plastic and Cosmetic Surgery The First Clinical Medical College of Southern Medical UniversityGuangzhou510080China Department of Dermatology The Second Affiliated HospitalGuangzhou University of Chinese MedicineGuangdong Provincial Hospital of Chinese MedicineGuangzhou510120China

The diabetic ulcer is one of the serious complications of *** this study,we aimed to establish an exosomal microRNA(miRNA)-targetedmessenger RNA(mRNA)regulatory network for screening new biomarkers for diabetic ulcer *** this purpose,exosomes were extracted from bone marrow stem cells(BMSCs)collected from diabetic ulcer patients and healthy *** miRNAs in exosomes was detected by high-throughput sequencing *** Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the differential miRNAs were *** miRNA-mRNA regulatory network between candidate miRNAs and their target genes were constructed by Cytoscape software basing on mRNA expression profiles data of diabetic ulcer patients from Gene Expression Omnibus(GEO).GO and KEGG analyses of the core genes were performed.A total of 63 differential expressed miRNAs in BMSCs exosomes were identified between diabetic ulcer patients and healthy *** GO analysis of miRNAs showed that it was mainly related to signal transduction and intercellular transport,and KEGG analysis showed that it was related to the vascular endothelial growth factor(VEGF)signaling *** core genes of the miRNA-mRNA network were thioredoxin interacting protein(TXNIP),cell division cycle 14A(CDC14A),cache domain containing 1(CACHD1),interferon-induced protein 44 like(IFI44L),late cornified envelope 1AL(CE1A),leucine-rich repeats and immunoglobulin-like domains 2(LRIG2),palmdelphin(PALMD)and serine and arginine-rich splicing factor 11(SRSF11).GO analysis of the core genes was related to platelet-derived growth factor receptor signaling *** KEGG analysis of the core genes was related to the cell cycle and nucleotide-binding oligomerization domain(NOD)-like receptor signaling pathway.A potential miRNA-mRNA regulatory network provides a comprehensive understanding of the molecular mechanisms and promising new targets such as miR-130a-5p,SESN2,LRIG2,and CDC1

关键词： Exosome Diabetic ulcer Angiogenesis Biological analysis miRNA

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Mechanisms of migration and invasion promoted by NSCLC cells-derived exosomes

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中国药理学与毒理学杂志 2019年第10期 881-881页

作者： GUO Qiao-ru HUANG Wen-jing YAN Yan-yan LIU Yun LIN Min-ting LI Jia-jun SU Chao-yue ZHANG Jian-ye guangdong provincial key laboratory of molecular target & Clinical Pharmacology School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Institute of Respiratory and Occupational Diseases Collaborative Innovation Center for Cancer Medical CollegeShanxi Datong University

OBJECTIVE To explore the function and mechanism of exosomes from non-small cell lung cancer(NSCLC) in promoting the invasion and metastasis of lung cancer cel s. METHODS The exosomes were isolated and identified by differential centrifugation, nanosight,transmission electron microscope and Western *** of the exosome uptake was applied by immune fluorescent confocal experiments. Scratch test was used to detect the influence of exosomes to tumor cells migration ability and transwell assay were carried out to investigate the effect of exosomes on migration and invasion. Total RNAs from exosomes were used for miRNA library preparation and sequencing. RT-Q-PCR was employed to detect the miRNA levels. Western blotting was adopted to detect the protein expression levels and dual luciferase reporter assay was used to verify the predict target site of miRNA. RESULTS The extracellular vesicles in the supernatant of NSCLC cells were isolated by the differential centrifugation and confirmed as exosomes by nanosight, transmission electron microscope and Western blotting. Exosomes from NSCLC can promote migration and invasion of non-small cell lung cancer cells showing concentration-and time-dependent manner. By analyzing the differential expression profile of exosomes miRNA of lung epithelial cells and lung cancer cell A549,30 miRNAs were screened out. Then, hsa-miR-34c-3p was selected in combination with clinical specimen detection. The expression level of miR-34c-3p in exosomes from lung cancer was lower than that of the normal *** Exosomes from NSCLC cells can be uptaken by cells and promote cell migration and invasion in dose-dependent manner. The expression level of miR-34c-3p in exosomes from NSCLC is significantly lower than normal tissues. The level of miR-34c-3p was further declined after incubating with exosomes. Exosomes from NSCLC cells can deliver miR-34c-3p to recepted cells and up-regulate the protein level of integrin α2β1.

关键词： NSCLC exosomes microRNA migration invasion

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