Fan Xingchen, Zou Xuan, Liu Cheng, Liu Jiawen, Peng Shuang, Zhang Shiyu, Zhou Xin, Wang Tongshan, Geng Xiangnan, Song Guoxin, Zhu Wei
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
First Clinical College of Nanjing Medical University, Nanjing, China.
Front Mol Biosci. 2022 May 31;9:888020. doi: 10.3389/fmolb.2022.888020. eCollection 2022.
MicroRNA (miRNA) binds to target mRNA and inhibit post-transcriptional gene expression. It plays an essential role in regulating gene expression, cell cycle, and biological development. This study aims to identify potential miRNA-mRNA regulatory networks that contribute to the pathogenesis of lung squamous cell carcinoma (LUSC). MiRNA microarray and RNA-Seq datasets were obtained from the gene expression omnibus (GEO) databases, the cancer genome atlas (TCGA), miRcancer, and dbDEMC. The GEO2R tool, "limma" and "DEseq" R packages were used to perform differential expression analysis. Gene enrichment analysis was conducted using the DAVID, DIANA, and Hiplot tools. The miRNA-mRNA regulatory networks were screened from the experimentally validated miRNA-target interactions databases (miRTarBase and TarBase). External validation was carried out in 30 pairs of LUSC tissues by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) were conducted to evaluate the diagnostic value. Clinical, survival and phenotypic analysis of miRNA-mRNA regulatory networks were further explored. We screened 5 miRNA and 10 mRNA expression datasets from GEO and identified 7 DE-miRNAs and 270 DE-mRNAs. After databases screening and correlation analysis, four pairs of miRNA-mRNA regulatory networks were screened out. The miRNA-mRNA network of miR-205-5p (up) and PTPRM (down) was validated in 30 pairs of LUSC tissues. MiR-205-5p and PTPRM have good diagnostic efficacy and are expressed differently in different clinical features and are related to tumor immunity. The research identified a potential miRNA-mRNA regulatory network, providing a new way to explore the genesis and development of LUSC.
微小RNA(miRNA)与靶mRNA结合并抑制转录后基因表达。它在调节基因表达、细胞周期和生物发育中起着至关重要的作用。本研究旨在识别有助于肺鳞状细胞癌(LUSC)发病机制的潜在miRNA-mRNA调控网络。从基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)、miRcancer和dbDEMC中获取miRNA微阵列和RNA测序数据集。使用GEO2R工具、“limma”和“DEseq”R包进行差异表达分析。使用DAVID、DIANA和Hiplot工具进行基因富集分析。从经过实验验证的miRNA-靶标相互作用数据库(miRTarBase和TarBase)中筛选miRNA-mRNA调控网络。通过实时定量逆转录PCR(qRT-PCR)在30对LUSC组织中进行外部验证。进行受试者工作特征曲线(ROC)和决策曲线分析(DCA)以评估诊断价值。进一步探索miRNA-mRNA调控网络的临床、生存和表型分析。我们从GEO中筛选了5个miRNA和10个mRNA表达数据集,并鉴定出7个差异表达miRNA(DE-miRNA)和270个差异表达mRNA(DE-mRNA)。经过数据库筛选和相关性分析,筛选出四对miRNA-mRNA调控网络。miR-205-5p(上调)和PTPRM(下调)的miRNA-mRNA网络在30对LUSC组织中得到验证。MiR-205-5p和PTPRM具有良好的诊断效能,在不同临床特征中表达不同,且与肿瘤免疫相关。该研究确定了一个潜在的miRNA-mRNA调控网络,为探索LUSC的发生和发展提供了新途径。