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结直肠癌中功能分子的综合生物信息学分析

Comprehensive bioinformatics analysis of functional molecules in colorectal cancer.

作者信息

Meng Tao, Lan Zhangzhang, Zhao Xiaoling, Niu Li, Chen Chuan, Zhang Wenyong

机构信息

Department of Gastrointestinal Surgery, Xinjiang Medical University Tumor Hospital, Urumqi, China.

School of Medicine, Southern University of Science and Technology, Shenzhen, China.

出版信息

J Gastrointest Oncol. 2022 Feb;13(1):231-245. doi: 10.21037/jgo-21-921.

Abstract

BACKGROUND

Colorectal cancer (CRC) is the 3rd most common cancer and the 2nd leading cause of cancer-related death. Numerous studies have found that aberrations in cellular molecules play an important role in the development of tumors. Studying and determining the interactions between these molecules can contribute to the diagnosis, treatment, and prognosis of tumors.

METHODS

The GSE151021, GSE156720, and GSE156719 data sets were analyzed to screen the differentially expressed messenger RNAs (DEmRNAs), long non-coding RNAs (DElncRNAs), and microRNAs (DEmiRNAs) in CRC. Database for Annotation, Visualization and Integrated Discovery (DAVID) and the Search Tool for the Retrieval of Interacting Genes/Proteins software were used to examine gene enrichment and the hub genes. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN was used to verify the expression of the hub genes. To analyze the overall survival (OS) of the hub genes, Kaplan-Meier plotter (KM plotter) was performed. Finally, the miRCancer database, TargetScan, and GSE156719 were used to identify the targets of the identified miRNAs. To predict the lncRNA-miRNA interactions, we used DIANA-LncBase v2 and GSE156720. Finally, the visualization protein‑protein interaction (PPI), competitive endogenous RNA (ceRNA) network was constructed using Cytoscape v3.1.

RESULTS

By analyzing GSE151021 and GSE156720, 23 upregulated mRNAs and 10 downregulated mRNAs were identified as sharing the differentially expressed genes (DEGs) between CRC and adjacent tissues. Furthermore, nucleolar protein 14 (), the sonic hedgehog () signaling molecule, phorbol-12-myristate-13-acetate-induced protein 1 (), the BCL2 apoptosis regulator (), and zinc finger E-box binding homeobox 2 () were considered hub genes. The constructed lncRNA-miRNA-mRNA network revealed 7 intersecting miRNAs (4 upregulated and 3 downregulated), 79 lncRNAs (40 upregulated and 39 downregulated), and 5 mRNAs (3 upregulated and 2 downregulated). Finally, we determined that the dysregulation of lncRNAs, such as , and , secluded altered the expression of several miRNAs, such as , , , and , and affected the occurrence and development of CRC.

CONCLUSIONS

We identified a series of DElncRNAs, DEmRNAs, and DEmiRNAs in CRC that might be considered potential biomarkers in understanding the complex molecular pathways leading to CRC development.

摘要

背景

结直肠癌(CRC)是第三大常见癌症,也是癌症相关死亡的第二大主要原因。众多研究发现,细胞分子异常在肿瘤发展中起重要作用。研究并确定这些分子之间的相互作用有助于肿瘤的诊断、治疗和预后。

方法

分析GSE151021、GSE156720和GSE156719数据集,以筛选结直肠癌中差异表达的信使核糖核酸(DEmRNAs)、长链非编码核糖核酸(DElncRNAs)和微小核糖核酸(DEmiRNAs)。使用注释、可视化和综合发现数据库(DAVID)以及检索相互作用基因/蛋白质的搜索工具软件来检查基因富集和枢纽基因。使用基因表达谱交互式分析2(GEPIA2)和UALCAN来验证枢纽基因的表达。为了分析枢纽基因的总生存期(OS),进行了Kaplan-Meier绘图仪(KM绘图仪)分析。最后,使用miRCancer数据库、TargetScan和GSE156719来鉴定已鉴定的miRNAs的靶标。为了预测lncRNA-miRNA相互作用,我们使用了DIANA-LncBase v2和GSE156720。最后,使用Cytoscape v3.1构建可视化蛋白质-蛋白质相互作用(PPI)、竞争性内源性RNA(ceRNA)网络。

结果

通过分析GSE151021和GSE156720,鉴定出23个上调的mRNAs和10个下调的mRNAs为结直肠癌与相邻组织之间共享的差异表达基因(DEGs)。此外,核仁蛋白14、音猬因子信号分子、佛波醇-12-肉豆蔻酸酯-13-乙酸诱导蛋白1、BCL2凋亡调节因子和锌指E盒结合同源框2被认为是枢纽基因。构建的lncRNA-miRNA-mRNA网络揭示了7个相交的miRNAs(4个上调和3个下调)、79个lncRNAs(40个上调和39个下调)和5个mRNAs(3个上调和2个下调)。最后,我们确定lncRNAs如[具体名称未给出]的失调改变了几种miRNAs如[具体名称未给出]的表达,并影响了结直肠癌的发生和发展。

结论

我们在结直肠癌中鉴定出一系列DElncRNAs、DEmRNAs和DEmiRNAs,它们可能被视为理解导致结直肠癌发展的复杂分子途径的潜在生物标志物。

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