Tumor-secreted miR-214 induces regulatory T cells： a major link between immune evasion and tumor growth.pdf

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Tumor-secreted miR-214 induces regulatory T cells： a major link between immune evasion and tumor growth.pdf

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CellResearch(2014)24：1164·1180． @2014IBCB。SIBS，CAS Allrightsreserved10010·602／14 ORIGINALARTICLE Tumor—secretedmiR-214inducesregulatoryTcells：a majorlinkbe eenimmuneevasionandtumorgrowth YuanYin’b=，XingCai，’，XiChen’，Hongw．eiLiang，，YujingZhang，JingLi，ZuoyunWang，XiulanChen， WenZhang，SeijiYokoyama4，ChengWang，LiangLi，LiminLi，DongxiaHou，LeiDong，TaoXu， TakachikaHiroi4FuquanYang~HongbinJi，JunfengZhang，KeZen ，Chen—YuZhang ，， diangsuEngineeringResearchCenterforMicroRNABiologyandBiotechnoloyg (JERC-MBB)，StateKeyLaboratoryofPhar- maceuticalBiotechnology,SchoolofLfieSciences,NanjingUniversity,22HankouRoad,Nanjing,Jiangsu210093，China,estate KeyLaboratoryofCellBioloyg,InstituteofBiochemistryandCellBioloyg,ShanghaiInstitutesfo，．BiologicalSciences,Chinese AcademyofSciences,320Yue．YangRoad,Shanghai200031．China,3KeyLaboratoryofProteinandPeptidePharmaceuticals＆ LaboratoryofProteomics．InstituteofBiophysics．ChineseAcademyo{Sciences．Bejiing1001O1．China,÷DepartmentOfAllergy andImmunology, 8 kyDMetropolitanInstituteofMedicalScience，Tokyo156．8506，Japan；5NationalLaboratoryofBiomac． romolecules，InstituteofBiophysics，ChineseAcademyofSciences，Beijing100101，China；WuxiOncologyInstitute，theAffiliated HospitalofJiangNanUniversiyt,Wuxi,Jiangsu214062,China AnincreasedpopulationofCD4CD25highFoxp3regulatoryTcells(Tregs)inthetumor-associatedmieroenvi- ronmentplaysanimportantroleincancerimmuneevasion．However,theunderlyingmechanism remainsunclear． Hereweobservedanincreasedsecretionofm iR-214invarioustypesofhumancancersandmousetumormodels． Tumor-secretedmiR-214wassufficientlydeliveredintorecipientTcellsbymicrovesicles(MVs)．Intargetedmouse peripheralCD4TceHs，tumor-derivedmiR-214efficientlydownregulatedphosphataseandtensinhomolog(PTEN) andpromotedTregexpansion．ThemiR一214-inducedTregssecreted higherlevelsofIL-10andpromotedt