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微阵列数据分析鉴定肺腺癌中的 miRNA 生物标志物并构建 lncRNA-miRNA-mRNA 网络。

Microarray data analysis to identify miRNA biomarkers and construct the lncRNA-miRNA-mRNA network in lung adenocarcinoma.

机构信息

Department of Public Health Medicine, University of Pécs Medical School, Szigeti str 12, Pécs 7624, Hungary.

Department of Thermophysiology, Institute for Translational Medicine, Medical School, University of Pécs, Szigeti str 12, Pécs 7624, Hungary.

出版信息

Medicine (Baltimore). 2022 Sep 9;101(36):e30393. doi: 10.1097/MD.0000000000030393.

Abstract

MicroRNAs (miRNAs), regulatory noncoding RNAs, are involved in gene regulation and may play a role in cancer development. The aim of this study was to identify miRNAs involved in lung adenocarcinoma (LUAD) using bioinformatics analysis. MiRNA (GSE135918), mRNA (GSE136043) and lncRNA (GSE130779) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed miRNAs (DEMis), mRNAs (DEMs), and lncRNA (DELs) in LUAD. We used DEMs for functional enrichment analysis. MiRNA expression quantification from The Cancer Genome Atlas (TCGA) was used to validate DEMis. LncBase Predicted v.2, Targetscan, and MiRBase were used to predict lncRNAs and mRNAs. The LUAD data in TCGA were used for overall survival (OS) analysis. We screened the downregulation of 8 DEMis and upregulation of 6 DEMis, and found that 70 signal pathways changed. We chose 3 relevant signaling pathways in lung cancer development, WNT, PI3K-Akt, and Notch, and scanned for mRNAs involved in them that are potential targets of these miRNAs. Then a lncRNA-miRNA-mRNA network was constructed. We also found 7 miRNAs that were associated with poor OS in LUAD. Low expression level of hsa-miR-30a was highly associated with poor OS in LUAD (P < .001) and the target genes of hsa-miR-30a-3p were abundant in the Wnt and AKT signaling pathways. In addition, our results reported for the first time that hsa-miR-3944 and hsa-miR-3652 were highly expressed in LUAD. And the high expression level of hsa-miR-3944 was associated with poor OS (P < .05). Hsa-miR-30a-3p may suppress the occurrence and progression of lung cancer through Wnt and AKT signaling pathways and become a good biomarker in LUAD. Hsa-miR-3944 and hsa-miR-3652 may serve as new biomarkers in LUAD.

摘要

微小 RNA(miRNAs)是一种调控非编码 RNA,参与基因调控,可能在癌症发生发展中发挥作用。本研究旨在通过生物信息学分析鉴定肺腺癌(LUAD)相关的 miRNAs。从基因表达综合数据库(GEO)下载 miRNA(GSE135918)、mRNA(GSE136043)和 lncRNA(GSE130779)微阵列数据集,以鉴定 LUAD 中差异表达的 miRNAs(DEMis)、mRNAs(DEMs)和 lncRNA(DELs)。我们使用 DEMs 进行功能富集分析。使用癌症基因组图谱(TCGA)中的 miRNA 表达定量数据来验证 DEMis。LncBase Predicted v.2、Targetscan 和 MiRBase 用于预测 lncRNA 和 mRNA。TCGA 中的 LUAD 数据用于总生存(OS)分析。我们筛选出下调的 8 个 DEMis 和上调的 6 个 DEMis,发现 70 个信号通路发生变化。我们选择与肺癌发生发展相关的 3 个信号通路(WNT、PI3K-Akt 和 Notch),扫描其中受这些 miRNA 调控的潜在靶基因。然后构建 lncRNA-miRNA-mRNA 网络。我们还发现了 7 个与 LUAD 不良 OS 相关的 miRNAs。hsa-miR-30a 的低表达水平与 LUAD 的不良 OS 高度相关(P < .001),并且 hsa-miR-30a-3p 的靶基因在 Wnt 和 AKT 信号通路中丰富。此外,我们的研究结果首次报道 hsa-miR-3944 和 hsa-miR-3652 在 LUAD 中高表达。并且 hsa-miR-3944 的高表达水平与不良 OS 相关(P < .05)。hsa-miR-30a-3p 可能通过 Wnt 和 AKT 信号通路抑制肺癌的发生和发展,成为 LUAD 的良好生物标志物。hsa-miR-3944 和 hsa-miR-3652 可能成为 LUAD 的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/10980501/805e5dcd088a/medi-101-e30393-g001.jpg

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