转录组测序分析糖尿病对小鼠AOM/DSS诱导结直肠癌发生的影响  

Transcriptomic high-throughput sequencing of AOM/DSS-induced colorectal carcinogenesis in mouse models with diabetes mellitus

作　　者：田旷怡 林志玲 许稷豪 于涛[1] 陈其奎[1] 黎洁瑶[1] Tian Kuangyi;Lin Zhiling;Xu Jihao;Yu Tao;Chen Qikui;Li Jieyao(Department of Gastroenterology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院消化内科,广州510120

出　　处：《新医学》2020年第5期340-347,共8页Journal of New Medicine

基　　金：广东省自然科学基金(2017A030313647);广州市科技计划项目(201903010064)。

摘　　要：目的探讨糖尿病(DM)对小鼠化学诱导结直肠癌发生的影响。方法采用氧化偶氮甲烷/葡聚糖硫酸钠诱导db/db小鼠和野生型(WT)小鼠产生结直肠癌,通过Illumina高通量测序技术筛选DM组与非DM组小鼠结肠肿瘤癌旁组织之间的差异表达基因,并对差异表达基因进行基因本体(GO)、京都基因与基因组百科全书(KEGG)功能注释与富集分析。结果与WT小鼠相比,DM小鼠结直肠的平均肿瘤体积增加(P <0.05)。DM小鼠与WT小鼠共有1656个差异表达基因(q <0.05),其中有70个mRNA在整个实验过程中均差异表达,主要组织相容性复合体(MHC)Ⅱ类基因包括H2-Ea-ps、H2-Q1、H2-DMb2、H2-Q4均在DM小鼠中表达上调(q <0.05)。GO富集分析发现免疫反应的调控和激活途径、抗原加工与提呈途径、抗原结合是显著富集的类型(q <0.05)。KEGG富集分析发现与免疫反应相关的抗原加工与呈递是显著富集的类型(q<0.05)。结论 DM状态下,小鼠免疫反应激活,MHCⅡ类基因表达存在显著差异,可能参与促进结直肠癌的发生发展。Objective To investigate the effect of diabetes mellitus(DM) on the chemically-induced colorectal carcinogenesis in mouse modsels. Methods Both db/db(DM) and wild-type(WT) mice were treated with AOM/DSS to induce colorectal carcinogenesis. The differentially expressed genes between the DMCRC group and the WT-CRC group were identified using Illumina Hiseq sequencing systems. The functional enrichment analysis was mapped in gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway databases. Results Compared with the WT mice, DM mice presented with significantly enhanced average tumor volume(P < 0.05). A total of 1656 m RNAs were differentially expressed(all q < 0.05) between DM and WT mice, and 70 m RNAs were differentially expressed throughout the whole experiment. Major histocompatibility complex(MHC) classⅡ genes including H2-Ea-ps, H2-Q1, H2-DMb2 and H2-Q4 were all significantly up-regulated in DM mice(all q < 0.05). GO enrichment analysis demonstrated that regulation and activation of immune response, antigen processing and presentation, and antigen binding were significantly enriched(all q < 0.05). The KEGG pathway enrichment analysis revealed that the DEGs were significantly associated with antigen processing and presentation(q < 0.05). Conclusion Immune response can be activated in DM mice. The MHC classⅡ genes are significantly differentially expressed, which probably promotes the incidence and progression of colorectal cancer under DM state.

关 键 词：糖尿病 结直肠癌 小鼠模型 高通量测序 

分 类 号：R587.1[医药卫生—内分泌] R735.3[医药卫生—内科学]