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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。

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

机构信息

Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Cancer Biomark. 2024;39(3):197-210. doi: 10.3233/CBM-230125.

DOI:10.3233/CBM-230125
PMID:38108345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11091561/
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.

摘要

背景

miRNA 诱导的 mRNA 转录后调控在肿瘤的发生、发展和转移中起着至关重要的作用。本研究旨在鉴定胃腺癌（STAD）中显著的 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，筛选差异表达的 RNA 和 miRNA（DE-miRNA/DE-mRNA）。通过 Hiplot 和 DAVID-mirPath 进行功能富集分析。应用 Connectivity MAP 进行化合物预测。通过 TarBase 和 MiRTarBase 预测 miRNA-mRNA 轴。采用实时逆转录聚合酶链反应（RT-qPCR）对胃标本进行验证。通过接受者操作特征曲线和决策曲线分析测量 miRNA-mRNA 相互作用的诊断效果。还进行了临床和生存分析。采用 CIBERSORT 和 ESTIMATE 进行免疫微环境测量。

结果

共筛选出 228 个 DE-mRNA（105 个上调和 123 个下调）和 38 个 DE-miRNA（22 个上调和 16 个下调）。TarBase 和 MiRTarBase 共鉴定出 18 个 miRNA-mRNA 对，其中 12 个在 RT-qPCR 中得到验证。建立并验证了 miR-301a-3p/ELL2 和 miR-1-3p/ANXA2 的网络，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 轴可能影响肿瘤微环境。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/184dd4ad3844/cbm-39-cbm230125-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/16cbb2995a1d/cbm-39-cbm230125-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/c358619e1ee6/cbm-39-cbm230125-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/241d00b95036/cbm-39-cbm230125-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/5fcaa0bbca6a/cbm-39-cbm230125-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/ff8745d910e2/cbm-39-cbm230125-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/184dd4ad3844/cbm-39-cbm230125-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/16cbb2995a1d/cbm-39-cbm230125-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/c358619e1ee6/cbm-39-cbm230125-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/241d00b95036/cbm-39-cbm230125-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/5fcaa0bbca6a/cbm-39-cbm230125-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/ff8745d910e2/cbm-39-cbm230125-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1671/11091561/184dd4ad3844/cbm-39-cbm230125-g006.jpg

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