基于转录组学分析驴油生酮饮食下CT26^(+)结肠癌肿瘤的变化  

Transcriptomic Analysis of Changes in CT26^(+)Colon Cancer Tumors under Donkey Oil Ketogenic Diet

作　　者：张华宸 张宁 邢敬亚 谢兰 祁兴震 路侹 程杰 李兰杰 刘桂芹[1] ZHANG Huachen;ZHANG Ning;XING Jingya;XIE Lan;QI Xingzhen;LU Ting;CHENG Jie;LI Lanjie;LIU Guiqin(College of Agriculture,Liaocheng University,Shandong Engineering Technology Research Center of Efficient Breeding and Ecological Rearing of black Donkey,Shandong Province Donkey Industry Science and Technology Collaborative Innovation Center,Liaocheng 252059,China;Institute of Biopharmaceutical Research Liaocheng University,Liaocheng 252059,China;Equine Research Center,Inner Mongolia Key Laboratory of Equine Genetics,Breeding and Reproduction,College of Animal Science,Inner Mongolia Agricultural University,Hohhot 010018,China;Dong-E-E-Jiao Co.Ltd.,Liaocheng 252200,China)

机构地区：[1]聊城大学农学与农业工程学院,山东省黑毛驴高效繁育与生态饲养工程技术研究中心,山东省驴产业科技协同创新中心,山东聊城252059 [2]聊城大学生物制药研究院,山东聊城252059 [3]内蒙古农业大学动物科学学院,内蒙古自治区马属动物遗传育种与繁殖学重点实验室,内蒙古农业大学马属动物研究中心,内蒙古呼和浩特010018 [4]东阿阿胶股份有限公司,山东聊城252200

出　　处：《现代食品科技》2023年第6期18-26,共9页Modern Food Science and Technology

基　　金：山东省现代农业产业技术体系驴产业创新团队项目资助(SDAIT-27);山东省乡村振兴科技创新提振行动计划项目(2021TZXD012);聊城大学博士科研启动项目(318052120);聊城大学畜牧学学科开放课题(319312101-03)。

摘　　要：该研究旨在通过转录组测序技术筛选出驴油生酮饮食(DonkeyOilKetogeniDiet,DOKD)影响CT26^(+)结肠癌肿瘤生长的相关基因,挖掘对DOKD响应的基因及其代谢通路,为解析驴油生酮饮食抑制肿瘤生长的机制提供依据。该研究选取一致性较好的CT26^(+)结肠癌BALB/c模型小鼠,随机分为2组,每组3个重复,分别饲喂驴油生酮饮食(DOKD)与正常饮食(ND)。饲喂10d后处死摘取肿瘤组织,测量肿瘤的质量及体积,并利用RNA-Seq技术和生物信息分析方法进行转录组测序及结果分析。DOKD组与ND组小鼠体质量无显著差异,肿瘤明显小于ND组。与ND组相比,DOKD组共18个基因差异表达,其中12个DEGs上调,6个DEGs下调。这些DEGs注释到170条GO条目,其中生物过程(BP)类别124条,细胞组成(CC)类别2条,分子功能(MF)类别44条;涉及18条KEGG通路,主要富集在IL-17信号通路、趋化因子信号通路、细胞因子受体相互作用信号通路、肿瘤坏死因子信号通路等重要通路。此外,该研究通过Western blot进一步研究了TLR4/NF-κB信号通路在在肿瘤中的作用。综上,DOKD对CT26^(+)结肠癌肿瘤有明显抑制作用,该作用可能与IL-17信号通路、趋化因子信号通路、细胞因子受体相互作用信号通路、TNF信号通路等通路密切相关。Screening of the genes related to the donkey oil ketogenic diet(DOKD)that affects the growth of CT26^(+)colon cancer tumors using transcriptome sequencing technology was investigated in this study.Mining the genes and metabolic pathways that respond to DOKD provides a basis for analyzing the mechanism of DOKD in inhibiting tumor growth.BALB/c model mice with CT26^(+)colon cancer with high consistency were selected and randomly divided into two groups with three replicates,and they were fed either a DOKD or normal diet(ND).The animals were sacrificed after 10 days of treatment.Subsequently,the tumors were excised,and tumor weights and volumes were recorded for analysis.RNA-Seq technology and bioinformatic analysis were used for transcriptome sequencing and results analysis.No significant difference was found in the body weight between the DOKD and ND groups,and the tumors were significantly smaller in the DOKD than those in the ND group.Compared with the ND group,a total of 18 genes were differentially expressed in the DOKD group,of which 12 differentially expressed genes(DEGs)were upregulated,and 6 DEGs were down regulated.These DEGs were annotated into a total of 170 GO items,including 124 in the biological process category,44 in the molecular function category,and 2 in the cellular composition category.A total of 18 KEGG pathways were involved,mainly enriched in the interleukin(IL)-17 signaling,chemokine signaling,cytokine receptor interaction signaling,tumor necrosis factor signaling,and other important pathways.In addition,this study further examined the role of the TLR4/NF-κB signaling pathway in tumors using western blotting.In summary,DOKD has a significant inhibitory effect on CT26^(+)colon cancer tumors,and this effect may be closely related to the IL-17,chemokine,cytokine receptor interaction,and tumor necrosis factor signaling pathways,among others.

关 键 词：驴油生酮饮食 肿瘤 转录组学 CT26^(+)结肠癌 

分 类 号：TS225.2[轻工技术与工程—粮食、油脂及植物蛋白工程] TS201.4[轻工技术与工程—食品科学与工程] R735.3[医药卫生—肿瘤]