探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）表达下调对结肠癌细胞衰老的意义和调控机制。

收集2022年1月至2024年12月在新疆自治区人民医院胃肠外科就诊的结肠癌患者的癌组织标本50例，同时收集癌旁组织标本50例，每组筛选5例标本进行转录组测序，筛选差异表达基因和蛋白。在培养箱内对结肠癌细胞HCT116细胞孵育及传代，分为对照组（不做任何处理）、IGF2BP3干扰组、IGF2BP3干扰空载组3组，HCT116细胞进行IGF2BP3干扰质粒及空载转染，转染后通过Trenswell检测观察HCT116细胞的侵袭能力，流式细胞术进行活性氧表达水平的检测，酶联免疫吸附分析法检测细胞上清中趋化因子（C-X-C基序）配体8（CXCR8）、转化生长因子-β（TGF-β）、白细胞介素（IL）-17、IL-6、人可溶性细胞间粘附因子1（siCAM-1）的含量，透射电镜观察不同组细胞形态变化，实时定量聚合酶链式反应和Western blot法检各组中IGF2BP3的基因和蛋白表达量，免疫组化检测结肠癌组织和癌旁组织中IGF2BP3的表达量。多组之间的比较采用单因素方差分析，组间两两比较采用非配对t检验。

与癌旁组织相比，肿瘤组织中差异表达基因有821个，其中上调基因有485个，下调基因有336个。上调表达显著性最高的5个基因分别是SIM2、ANKRD18EP、IGKV1D-8、MMP3、CYP24A1；下调表达显著性最高的5个基因分别是CMAHP、LINC02490、G6PC1、PTPRQ、LGSN。生物学过程分析显示这些差异表达基因主要在细胞过程、生物调节、代谢过程、细胞部分、膜、细胞器、细胞部分、细胞器、膜、细胞器部分、膜部分、含蛋白质复合物、细胞外区域部分、细胞外区域等发挥作用。KEGG通路聚类疾病类型主要聚在内分泌代谢疾病、癌性疾病、免疫性疾病、消化系统、免疫系统、内分泌系统、细胞生长与死亡、脂质代谢、复制和修复等通路。细胞实验结果显示，与对照组相比，在IGF2BP3干扰组细胞侵袭能力显著降低（P<0.01），活性氧水平升高，CXCR8、TGF-β、IL-17、IL-6、siCAM-1含量明显降低（P均<0.05），IGF2BP3基因和蛋白表达量明显降低（P<0.01）。

结肠癌组织表达的基因富集在DNA复制、细胞周期、神经活性配体-受体相互作用、类风湿性关节炎、Wnt信号通路和IGF2BP3基因的相互作用可能通过调控细胞衰老导致结肠癌肿瘤微环境的变化，促进结肠癌的发生和发展。

To explore the significance and regulatory mechanism of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) expression in the senescence of colon cancer cells..

In order to facilitate comprehensive research, it is imperative to procure 50 tissue specimens from patients suffering from colon cancer, who have been attended to within our gastroenterology department between January 2022 and December 2024. Concomitantly, an equivalent number of contiguous tissue samples should be gathered.Subsequently, a subset consisting of 5 samples from each category should be earmarked for transcriptome sequencing, aimed at the identification and screening of differentially expressed genes and their corresponding proteins. HCT116 cells were incubated and passaged in an incubator, and HCT116 cell suspension was prepared for transfection. After transfection,they were divided into three groups:control group (without any treatment), IGF2BP3 interference group, and IGF2BP3 interference empty group. Cell migration assay (Trenswell) was used to detect the invasion ability of HCT116 cells, Detection of reactive oxygen species (ROS) expression levels using flow cytometry, ELISA was used to detect the content of CXCR8, transforming grouth factor-β(TGF-β), IL-17, IL-6, and soluble intercellular adhesion molecule siCAM-1 in the cell supernatant,transmission electron microscopy was used to observe the morphological changes of different groups of cells, RT-PCR and WB were used to detect the gene and protein expression levels of IGF2BP3 in each group, and immunohistochemistry was used to detect the expression of IGF2BP3 in colon cancer tissue and adjacent tissues. Expression level.

Compared with the adjacent tissues,there were 821 differentially expressed genes in the cancer tissue group,including 485 up-regulated genes and 336 down regulated genes.The five genes with the highest significant upregulation were SIM2 ANKRD18EP, IGKV1D-8, MMP3, CYP24A1, The 5 genes with the highest significant downregulation of expression are CMAHP LINC02490, G6PC1, PTPRQ, LGSN. Biological process analysis shows that these differentially expressed genes mainly function in cellular processes, biological regulation, metabolic processes, cell parts, membranes, organelles, cell parts, organelles, membranes, organelle parts, membrane parts, protein-containing complexes, extracellular region parts, and extracellular regions. KEGG pathway analysis mainly clusters the disease types in endocrine and metabolic diseases, cancer diseases, immune diseases, digestive system, immune system, endocrine system, cell growth and death, lipid metabolism, replication and repair, and other pathways. The cell experiment results showed that compared with the control group,the invasion ability of cells in the IGF2BP3 interference group was significantly reduced (P<0.01), the levels of reactive oxygen species were significantly elevated, the contents of CXCR8, TGF-β, IL-17, IL-6, and siCAM-1 were significantly reduced (all P<0.05), and the expression levels of IGF2BP3 gene and protein were significantly reduced (P<0.01).

The genes expressed in colon cancer tissues are enriched in DNA replication, cell cycle,neuroactive ligand receptor interactions, rheumatoid arthritis, and Wnt signaling pathways. The interaction between these signaling pathways and IGF2BP3 gene may regulate cellular aging, leading to changes in the tumor micro environment of colon cancer and promoting its occurrence and development.