Building endoplasmic reticulum stress-related LncRNAs signatures of lung adenocarcinoma

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-08-15 DOI:10.1002/jgm.3731

Kai Chen, Peiling Dai, Lizhong Gu

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引用次数: 0

Abstract

Background

Endoplasmic reticulum stress (ERS) could be a strategy for treating malignant tumors. Moreover, long noncoding RNAs (lncRNAs) can promote tumorigenesis and progression, and forecast the prognosis of cancers. Nevertheless, the prognostic value of ERS-related lncRNAs has not been reported in lung adenocarcinoma (LUAD).

Methods

The messenger RNA (mRNA), microRNA (miRNA) and lncRNA expression data related to LUAD were obtained in public databases (TCGA and GEO databases). Prognostic ERS-related differentially expressed lncRNAs (ERS-DELs) were obtained and used to build an ERS-related model by Cox regression analysis. Moreover, we further screened independent prognostic elements and built a nomogram. Furthermore, enrichment analysis of genes was conducted to investigate the functions. A lncRNA–miRNA–mRNA network was built to explore mechanism of lncRNAs. Finally, qRT-PCR was utilized to examine the expression levels of lncRNAs.

Results

30 ERS-DELs were identified, and an ERS-related signature was built based on AF131215.2, LINC00472, LINC01352, RP1-78O14.1, RP11-253E3.3, RP11-98D18.9, and SNHG12. Gene set enrichment analysis indicated that genes in the high-risk group were chiefly focused on the regulation of mRNA binding, and genes in the low-risk group were significantly focused on protein localization to cilia. A lncRNA–miRNA–mRNA network, containing 7 signature lncRNAs, 23 miRNAs, and 128 mRNAs, was also established. Eventually, quantitative real-time polymerase chain reaction was used to confirm that seven prognostic lncRNAs had a consistent expression with the analysis.

Conclusions

An ERS-related signature containing seven prognostic lncRNAs was built, which offered new thinking concerning the role of ERS-related lncRNAs in LUAD.

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构建肺腺癌的内质网应激相关 LncRNAs 特征

背景：内质网应激（ERS）可能是治疗恶性肿瘤的一种策略。此外，长非编码 RNA（lncRNA）可促进肿瘤的发生和发展，并预测癌症的预后。然而，肺腺癌（LUAD）中与ERS相关的lncRNAs的预后价值尚未见报道：方法：从公共数据库（TCGA 和 GEO 数据库）中获取与 LUAD 相关的信使 RNA（mRNA）、microRNA（miRNA）和 lncRNA 表达数据。通过Cox回归分析，获得了预后性ERS相关的差异表达lncRNAs（ERS-DELs），并用于建立ERS相关模型。此外，我们还进一步筛选了独立的预后要素，并建立了一个提名图。此外，我们还对基因进行了富集分析，以研究其功能。我们建立了一个 lncRNA-miRNA-mRNA 网络，以探索 lncRNA 的作用机制。最后，利用qRT-PCR检测了lncRNAs的表达水平：结果：发现了30个ERS-DELs，并根据AF131215.2、LINC00472、LINC01352、RP1-78O14.1、RP11-253E3.3、RP11-98D18.9和SNHG12建立了ERS相关特征。基因组富集分析表明，高风险组的基因主要集中在 mRNA 结合的调控上，而低风险组的基因则主要集中在纤毛蛋白质定位上。此外，还建立了一个包含7个特征性lncRNA、23个miRNA和128个mRNA的lncRNA-miRNA-mRNA网络。最后，研究人员利用定量实时聚合酶链反应证实，7个预后lncRNA的表达与分析结果一致：结论：建立了包含7个预后lncRNA的ERS相关特征，为ERS相关lncRNA在LUAD中的作用提供了新思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.