Construct dysregulated miRNA-mRNA interaction networks to conjecture possible pathogenesis for Stomach adenocarcinomas.

IF 2.2 4区医学 Q3 ONCOLOGY Cancer Biomarkers Pub Date : 2024-01-01 DOI:10.3233/CBM-230125

Shuang Peng, Hao Zhang, Guoxin Song, Jingfeng Zhu, Shiyu Zhang, Cheng Liu, Feng Gao, Hang Yang, Wei Zhu

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Abstract

Background: Post-transcriptional regulation of mRNA induced by microRNA is known crucial in tumor occurrence, progression, and metastasis. This study aims at identifying significant miRNA-mRNA axes for stomach adenocarcinomas (STAD).

Method: RNA expression profiles were collected from The Cancer Genome Atlas (TCGA) and GEO database for screening differently expressed RNAs and miRNAs (DE-miRNAs/DE-mRNAs). Functional enrichment analysis was conducted with Hiplot and DAVID-mirPath. Connectivity MAP was applied in compounds prediction. MiRNA-mRNA axes were forecasted by TarBase and MiRTarBase. Real-time reverse transcription polymerase chain reaction (RT-qPCR) of stomach specimen verified these miRNA-mRNA pairs. Diagnosis efficacy of miRNA-mRNA interactions was measured by Receiver operation characteristic curve and Decision Curve Analysis. Clinical and survival analysis were also carried out. CIBERSORT and ESTIMATE was employed for immune microenvironment measurement.

Result: Totally 228 DE-mRNAs (105 upregulated and 123 downregulated) and 38 DE-miRNAs (22 upregulated and 16 downregulated) were considered significant. TarBase and MiRTarBase identified 18 miRNA-mRNA pairs, 12 of which were verified in RT-qPCR. The network of miR-301a-3p/ELL2 and miR-1-3p/ANXA2 were established and verified in external validation. The model containing all 4 signatures showed better diagnosis ability. Via interacting with M0 macrophage and resting mast cell, these miRNA-mRNA axes may influence tumor microenvironment.

Conclusion: This study established a miRNA-mRNA network via bioinformatic analysis and experiment validation for STAD.

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构建失调的 miRNA-mRNA 相互作用网络，推测胃腺癌的可能发病机制。

背景：众所周知，由microRNA诱导的mRNA转录后调控对肿瘤的发生、发展和转移至关重要。本研究旨在确定胃腺癌（STAD）的重要 miRNA-mRNA 轴：方法：从癌症基因组图谱（TCGA）和 GEO 数据库中收集 RNA 表达谱，筛选不同表达的 RNA 和 miRNA（DE-miRNAs/DE-mRNAs）。利用 Hiplot 和 DAVID-mirPath 进行了功能富集分析。在化合物预测中应用了连接性 MAP。用 TarBase 和 MiRTarBase 预测了 MiRNA-mRNA 轴。胃标本的实时逆转录聚合酶链反应（RT-qPCR）验证了这些 miRNA-mRNA 对。miRNA-mRNA相互作用的诊断效果通过接收者操作特征曲线和决策曲线分析进行测量。此外，还进行了临床和生存分析。免疫微环境测量采用了 CIBERSORT 和 ESTIMATE：结果：共有228个DE-mRNA（105个上调，123个下调）和38个DE-miRNA（22个上调，16个下调）被认为具有重要意义。TarBase和MiRTarBase发现了18对miRNA-mRNA，其中12对在RT-qPCR中得到验证。建立了 miR-301a-3p/ELL2 和 miR-1-3p/ANXA2 网络，并在外部验证中得到验证。包含所有 4 个特征的模型显示出更好的诊断能力。通过与M0巨噬细胞和静止肥大细胞相互作用，这些miRNA-mRNA轴可能会影响肿瘤微环境：本研究通过生物信息学分析和实验验证建立了 STAD 的 miRNA-mRNA 网络。

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来源期刊

Cancer Biomarkers ONCOLOGY-

CiteScore

5.20

自引率

3.20%

发文量

195

审稿时长

3 months

期刊介绍： Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.