TRIM21在结肠炎相关的癌症中 [复制链接]

TRIM21IsDecreasedinColitis-associatedCancerandNegativelyRegulatesEpithelialCarcinogenesis

TRIM21在结肠炎相关的癌症中水平下降，并抑制上皮癌变。

Abstract

Backgroundripartitemotif-containing(TRIM)21isreportedtobeassociatedwiththeregulationofimmuneresponseingutmucosa.HerewestudiedtheunderlyingmechanismsofTRIM21inthepathogenesisofcolitis-associatedcancer(CAC).

背景：据报道，TRIM21与调节肠道黏膜免疫应答有关。在这里，我们研究了TRIM21在结肠炎相关癌症（CAC）发病机理中的潜在机制。

Methods:WeanalyzedTRIM21expressionintumortissuesfrompatientswithcolorectalcancer(CRC)andulcerativecolitis(UC)-associatedcancerbyimmunohistochemistryandreal-timepolymerasechainreactionandestablishedaCACmodelinTRIM21-∕-andwildtypemicebyazoxymethane(AOM)anddextransodiumsulfate(DSS).Associatedgeneexpressionoftumorcellproliferation,adhesion,tissueremodelingandangiogenesis,andinflammatorycytokineswereexaminedinnormalcolonandCACbyimmunohistochemistryandreal-timepolymerasechainreaction.

方法：我们通过免疫组化和实时聚合酶链反应分析了大肠癌（CRC）和UC相关癌患者肿瘤组织中TRIM21的表达情况，并对TRIM21-∕-和野生型小鼠进行AOM和DSS诱导，建立CAC模型。通过免疫组化和实时聚合酶链反应检测了正常结肠和CAC中肿瘤细胞增殖、黏附、组织重塑和血管生成以及炎性细胞因子的相关基因表达情况。

Results:ExpressionofTRIM21wasfoundtobedecreasedintumortissuesfrompatientswithCRCandUC-associatedcancerthanthatincontrols,andTRIM21-∕-deficiencypromotedAOM/DSS-inducedCAC,characterizedbymoreweightlossandmultiple,largecolontumorsinTRIM21-∕-mice.Moreover,associatedgeneexpressionoftumorcellproliferation(eg,Ki67),tissueremodelingandangiogenesis(eg,MMP10,HIF1-α,COX2,Ang4),andpro-inflammatorycytokines(eg,IL-6,TNF-α,IL-1β)markedlyupregulated,whereasassociatedgeneexpressionoftumorcelladhesion(E-cadherin)andinflammatorycytokines(eg,IL-10,TGF-β,Foxp3,IFN-γ)downregulatedintumortissuesfromTRIM21-/-mice