Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are...Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are not to be well studied.Here,we validated that the expression of miR-16-5p was decreased significantly in NSCLC samples and cell lines.The correlation between the clinicopathological features of NSCLC and the miR-16-5p expression showed that the expression of miR-16-5p in non-small cell lung cancer was linked with the advanced TNM stage,positive lymph node metastasis,with short overall survival(OS).Also,a negative correlation between miR-16-5p and Fermitin family member 2(FERMT2)was observed,implying there may be a potential link about their regulation.The hypothesis was further confirmed by in-silico analysis and dual-luciferase reporter assay.Moreover,we demonstrated that the transfections of miR-16-5p mimics could alter some biological characteristics of NSCLC cells remarkably accomplished by the expression variance of FERMT2 in vitro and in vivo assays.Summarily,this study demonstrated that miR-16-5p,as a tumor suppression factor in NSCLC by targeting FERMT2,could serve as one promising biomarker in the prediction for NSCLC patients.展开更多
Background Alzheimer’s disease(AD)is the most prominent form of dementia worldwide.It is characterized by tau lesions that spread throughout the brain in a spatio-temporal manner.This has led to the prion-like propag...Background Alzheimer’s disease(AD)is the most prominent form of dementia worldwide.It is characterized by tau lesions that spread throughout the brain in a spatio-temporal manner.This has led to the prion-like propagation hypothesis implicating a transfer of pathological tau seeds from cell to cell.Human brain-derived extracellular vesicles(BD-EVs)isolated from the brain-derived fluid of AD patients contain seeds that contribute to this tau pathology spreading.Knowing the rich diversity of EVs,isolation of functional EV sub-populations is required to unravel their implication in the pathophysiology of AD.Methods Here,enriched-small EVs(eSEVs)and enriched-large EVs(eLEVs)were isolated from frozen tissues after collagenase enzymatic brain dissociation to guarantee the best EVs’integrity.Then proteomic profiling and tau seeding capacity testing were performed in vitro and in vivo.Results BD-EVs were stratified according to their size(eSEVs and eLEVs)and characterized to define new markers specific to EVs in AD.Both AD-derived eSEVs and eLEVs show the presence of GWAS-associated proteins and indicate a specific AD pathophysiological signature.Notably,AD eSEVs contain more proteins relative to the integrin-mediated synaptic signaling,while AD eLEVs proteins were more related to respiratory electron transport and brain immunity.Injection of these vesicles in transgenic mouse brain revealed that the AD-derived eSEVs are more prone than eLEVs to participate in the prion-like propagation and hence represent an interesting therapeutic target.Conclusion This study highlights the significant contribution of AD-derived EVs to tau propagation and provides new insights into different roles of EV sub-populations in AD.展开更多
基金was supported by grants from the National Natural Science Foundation of China(No.81772281)the Shandong Province Taishan Scholar Project(No.ts201712067)+1 种基金the Major Research and Development Program of Shandong Province(No.2017GSF18124)the Natural Science Foundation of Shandong Province(No.ZR2020MH218).
文摘Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are not to be well studied.Here,we validated that the expression of miR-16-5p was decreased significantly in NSCLC samples and cell lines.The correlation between the clinicopathological features of NSCLC and the miR-16-5p expression showed that the expression of miR-16-5p in non-small cell lung cancer was linked with the advanced TNM stage,positive lymph node metastasis,with short overall survival(OS).Also,a negative correlation between miR-16-5p and Fermitin family member 2(FERMT2)was observed,implying there may be a potential link about their regulation.The hypothesis was further confirmed by in-silico analysis and dual-luciferase reporter assay.Moreover,we demonstrated that the transfections of miR-16-5p mimics could alter some biological characteristics of NSCLC cells remarkably accomplished by the expression variance of FERMT2 in vitro and in vivo assays.Summarily,this study demonstrated that miR-16-5p,as a tumor suppression factor in NSCLC by targeting FERMT2,could serve as one promising biomarker in the prediction for NSCLC patients.
基金supported by grants from the program Investissement d’Avenir LabEx(investing in the future laboratory excellence)DISTALZ(Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer’s Disease)+2 种基金France Alzheimer,Fondation pour la Recherche Medicale and ANR grants(TONIC,TauSeed)Our laboratories are also supported by LiCEND(Lille Centre of Excellence in Neurodegenerative Disorders)CNRS,Inserm,Metropole Europeenne de Lille,University of Lille,I-SITE ULNE,Region Hauts de France and FEDER.The OrganOmics platform of PRISM Inserm U1192 which is recognized and supported by the University of Lille and,the Infrastructure PROFI(https://www.profi prote omics.fr/)and the GIS IbiSA(https://www.ibisa.net/).The OrganOmics platform(Villeneuve d’Ascq,France)is also supported by Region Hauts de France and FEDER funding.
文摘Background Alzheimer’s disease(AD)is the most prominent form of dementia worldwide.It is characterized by tau lesions that spread throughout the brain in a spatio-temporal manner.This has led to the prion-like propagation hypothesis implicating a transfer of pathological tau seeds from cell to cell.Human brain-derived extracellular vesicles(BD-EVs)isolated from the brain-derived fluid of AD patients contain seeds that contribute to this tau pathology spreading.Knowing the rich diversity of EVs,isolation of functional EV sub-populations is required to unravel their implication in the pathophysiology of AD.Methods Here,enriched-small EVs(eSEVs)and enriched-large EVs(eLEVs)were isolated from frozen tissues after collagenase enzymatic brain dissociation to guarantee the best EVs’integrity.Then proteomic profiling and tau seeding capacity testing were performed in vitro and in vivo.Results BD-EVs were stratified according to their size(eSEVs and eLEVs)and characterized to define new markers specific to EVs in AD.Both AD-derived eSEVs and eLEVs show the presence of GWAS-associated proteins and indicate a specific AD pathophysiological signature.Notably,AD eSEVs contain more proteins relative to the integrin-mediated synaptic signaling,while AD eLEVs proteins were more related to respiratory electron transport and brain immunity.Injection of these vesicles in transgenic mouse brain revealed that the AD-derived eSEVs are more prone than eLEVs to participate in the prion-like propagation and hence represent an interesting therapeutic target.Conclusion This study highlights the significant contribution of AD-derived EVs to tau propagation and provides new insights into different roles of EV sub-populations in AD.
