Géczi Dóra, Klekner Álmos, Balogh István, Penyige András, Szilágyi Melinda, Virga József, Bakó Andrea, Nagy Bálint, Torner Bernadett, Birkó Zsuzsanna
Department of Human Genetics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Department of Neurosurgery, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Pharmaceuticals (Basel). 2025 Mar 19;18(3):431. doi: 10.3390/ph18030431.
(1) Glioblastoma (GBM) is one of the most aggressive brain tumors with a poor prognosis. Therefore, new insights into GBM diagnosis and treatment are required. In addition to differentially expressed mRNAs, miRNAs may have the potential to be applied as diagnostic biomarkers. (2) In this study, profiling of human miRNAs in combination with mRNAs was performed on total RNA isolated from tissue samples of five control and five GBM patients, using a high-throughput RNA sequencing (RNA-Seq) approach. (3) A total of 35 miRNAs and 365 mRNAs were upregulated, while 82 miRNAs and 1225 mRNAs showed significant downregulation between tissue samples of GBM patients compared to the control samples using the iDEP to analyze RNA-Seq data. To validate our results, the expression of five miRNAs (hsa-miR-196a-5p, hsa-miR-21-3p, hsa-miR-10b-3p, hsa-miR-383-5p, and hsa-miR-490-3p) and fourteen mRNAs (E2F2, HOXD13, VEGFA, CDC45, AURKB, HOXC10, MYBL2, FABP6, PRLHR, NEUROD6, CBLN1, HRH3, HCN1, and RELN) was determined by RT-qPCR assay. The miRNet tool was used to build miRNA-target interaction. Furthermore, a protein-protein interaction (PPI) network was created from the miRNA targets by applying the NetworkAnalyst 3.0 tool. Based on the PPI network, a functional enrichment analysis of the target proteins was also carried out. (4) We identified an miRNA panel and several deregulated mRNAs that could play an important role in tumor development and distinguish GBM patients from healthy controls with high sensitivity and specificity using total RNA isolated from tissue samples.
(1) 胶质母细胞瘤（GBM）是最具侵袭性的脑肿瘤之一，预后较差。因此，需要对GBM的诊断和治疗有新的见解。除了差异表达的mRNA外，miRNA也有可能被用作诊断生物标志物。(2) 在本研究中，使用高通量RNA测序（RNA-Seq）方法，对从5名对照和5名GBM患者的组织样本中分离的总RNA进行了人类miRNA与mRNA的联合分析。(3) 使用iDEP分析RNA-Seq数据，结果显示，与对照样本相比，GBM患者组织样本中共有35个miRNA和365个mRNA上调，而82个miRNA和1225个mRNA显著下调。为了验证我们的结果，通过RT-qPCR测定法确定了5个miRNA（hsa-miR-196a-5p、hsa-miR-21-3p、hsa-miR-10b-3p、hsa-miR-383-5p和hsa-miR-490-3p）和14个mRNA（E2F2、HOXD13、VEGFA、CDC45、AURKB、HOXC10、MYBL2、FABP6、PRLHR、NEUROD6、CBLN1、HRH3、HCN1和RELN）的表达。使用miRNet工具构建miRNA-靶标相互作用。此外，通过应用NetworkAnalyst 3.0工具，从miRNA靶标创建了蛋白质-蛋白质相互作用（PPI）网络。基于PPI网络，还对靶蛋白进行了功能富集分析。(4) 我们鉴定了一个miRNA组和几个失调的mRNA，它们可能在肿瘤发展中起重要作用，并使用从组织样本中分离的总RNA以高灵敏度和特异性区分GBM患者与健康对照。
