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长链非编码RNA作为胃癌潜在的生物标志物或治疗靶点

Long non-coding RNAs as potential biomarkers or therapeutic targets in gastric cancer.

作者信息

Askari Nahid, Salek Esfahani Behnaz, Parvizpour Sepideh, Shafieipour Sara, Hadizadeh Morteza

机构信息

Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, End of Haft Bagh-e-Alavi Highway, Kerman, Iran.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Gastroenterol Hepatol Bed Bench. 2023;16(3):297-306. doi: 10.22037/ghfbb.v16i2.2701.

Abstract

AIM

This study aimed to find lncRNAs and mRNAs that were expressed differently by combining microarray datasets from different studies. This was done to find important target genes in gastric cancer for anti-cancer therapy.

BACKGROUND

Gastric cancer (GC) is the fourth most frequent and second-most deadly malignancy worldwide. Thus, genetic diagnosis and treatment should focus on genetic and epigenetic variables. Based on several studies, disordered expression of non-coding RNAs (ncRNAs), such as lncRNAs, regulate gastric cancer invasion and metastasis. Besides, lncRNAs cooperatively regulate gene expression and GC progression.

METHODS

We obtained differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) from three GC tissue microarray datasets by meta-analysis and screened genes using the "Limma" package. Then, using the RNAInter database, we allocated DEmRNAs to each DElncRNA. ClusterProfiler and GOplot programs were used to analyze function enrichment pathways and gene ontologies for final DEmRNAs.

RESULTS

A total of 9 differentially expressed lncRNAs (DElncRNAs) (5 up-regulated and 4 down-regulated), and 856 DEmRNAs (451 up-regulated and 405 down-regulated) between tumor and adjacent normal samples were found. Finally, 117 differentially expressed mRNAs were predicted as interactors of six DElncRNAs (H19, WT1-AS, EMX2OS, HOTAIR, ZEB1-AS1, and LINC00261).

CONCLUSION

In order to promote cancer therapeutics and give knowledge on the process of carcinogenesis, our study projected a network of drug-gene interactions for discovered genes and presented relevant prospective biomarkers for the prognosis of patients with stomach cancer.

摘要

目的

本研究旨在通过合并来自不同研究的微阵列数据集,找出表达存在差异的长链非编码RNA(lncRNA)和信使核糖核酸(mRNA)。这样做是为了在胃癌中找到用于抗癌治疗的重要靶基因。

背景

胃癌(GC)是全球第四大常见且第二大致命的恶性肿瘤。因此,基因诊断和治疗应关注基因和表观遗传变量。基于多项研究,lncRNA等非编码RNA(ncRNA)的无序表达可调节胃癌的侵袭和转移。此外,lncRNA协同调节基因表达和胃癌进展。

方法

我们通过荟萃分析从三个胃癌组织微阵列数据集中获得差异表达的mRNA(DEmRNA)和lncRNA(DElncRNA),并使用“Limma”软件包筛选基因。然后,利用RNAInter数据库,将DEmRNA分配给每个DElncRNA。使用ClusterProfiler和GOplot程序分析最终DEmRNA的功能富集途径和基因本体。

结果

在肿瘤样本和相邻正常样本之间,共发现9个差异表达的lncRNA(5个上调和4个下调)以及856个DEmRNA(451个上调和405个下调)。最后,117个差异表达的mRNA被预测为6个DElncRNA(H19, WT1-AS, EMX2OS, HOTAIR, ZEB1-AS1和LINC00261)的相互作用分子。

结论

为了促进癌症治疗并提供有关致癌过程的知识,我们的研究针对发现的基因构建了药物-基因相互作用网络,并为胃癌患者的预后提供了相关的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49fa/10520387/07ca046fc4ef/GHFBB-16-297-g001.jpg

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