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基于计算方法构建 lncRNA/假基因-miRNA 网络,以鉴定糖酵解通路相关前列腺腺癌潜在生物标志物。

Construction of lncRNA/Pseudogene-miRNA Network Based on In Silico Approaches for Glycolysis Pathway to Identify Prostate Adenocarcinoma-Related Potential Biomarkers.

机构信息

Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Laboratory Science, Paramedical School, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Appl Biochem Biotechnol. 2024 Apr;196(4):2332-2355. doi: 10.1007/s12010-023-04617-4. Epub 2023 Aug 5.

Abstract

LncRNAs, pseudogenes, and miRNAs participate a fundamental function in tumorigenesis, metabolism, and invasion of cancer cells, although their regulation of tumor glycolysis in prostate adenocarcinoma (PRAD) is thoroughly not well studied. In this study, we applied transcriptomic, proteomic, and medical information to identify glycolysis-related key genes and modules associated with PRAD. Then, the glycolysis-related lncRNA/lncRNAs/pseudogenes-miRNA-mRNA network was constructed. Analysis of DNA methylation status and expression data determined a DNA methylation-dysregulated three-DE-mRNAs signature for predicting diagnosis, ANGPTL4, GNE, and HSPA in PRAD patients and healthy control. Several lncRNAs/pseudogenes, significantly correlated with the overall survival PVT1, CA5BP1, MIRLET7BHG, SNHG12, and ZNF37BP and disease-free survival status, MALAT1, GUSBP11, MIRLET7BHG, and SNHG1, of patients with PRAD were determined. The methylation profile of DE-lncRNA/pseudogenes was significantly proper for predicting PRAD prognostic model. The transcription level of 6 DE-mRNA ANGPTL4, QSOX1, BIK, CLDN3, DDIT4, and TFF3 was correlated with cancer-related fibroblast infiltration in PRAD. The mutated form of 7 mRNAs, COL5A1, IDH1, HK2, DDIT4, GNE, and QSOX1, was associated with PRAD. In addition to the glycolysis pathway, DE-RNAs play regulatory roles on several pathways, including DNA damage, RTK, cell cycle, RAS/MAPK, TSC/mTOR and PI3K/AKT, AR hormone, and EMT. Overall, our study improves our knowledge of the relation between lncRNAs/pseudogenes and miRNA related to glycolysis and PRAD pathogenesis.

摘要

LncRNAs、假基因和 miRNAs 参与肿瘤发生、代谢和癌细胞侵袭的基本功能,尽管它们在前列腺腺癌(PRAD)中的肿瘤糖酵解调控还没有得到深入研究。在这项研究中,我们应用转录组学、蛋白质组学和医学信息来识别与 PRAD 相关的糖酵解相关关键基因和模块。然后,构建了糖酵解相关 lncRNA/lncRNAs/pseudogenes-miRNA-mRNA 网络。分析 DNA 甲基化状态和表达数据确定了一个用于预测 PRAD 患者和健康对照的诊断、ANGPTL4、GNE 和 HSPA 的 DNA 甲基化失调的三-DE-mRNAs 特征。几个与总生存 PVT1、CA5BP1、MIRLET7BHG、SNHG12 和 ZNF37BP 以及 PRAD 患者无病生存状态显著相关的 lncRNAs/pseudogenes,MALAT1、GUSBP11、MIRLET7BHG 和 SNHG1 被确定。DE-lncRNA/pseudogenes 的甲基化谱显著适合预测 PRAD 预后模型。6 个 DE-mRNA ANGPTL4、QSOX1、BIK、CLDN3、DDIT4 和 TFF3 的转录水平与 PRAD 中的癌症相关成纤维细胞浸润相关。7 个 mRNAs(COL5A1、IDH1、HK2、DDIT4、GNE 和 QSOX1)的突变形式与 PRAD 相关。除了糖酵解途径外,DE-RNAs 还对包括 DNA 损伤、RTK、细胞周期、RAS/MAPK、TSC/mTOR 和 PI3K/AKT、AR 激素和 EMT 在内的几个途径发挥调节作用。总的来说,我们的研究提高了我们对 lncRNAs/pseudogenes 与糖酵解和 PRAD 发病机制相关的 miRNA 之间关系的认识。

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