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通过建立 ceRNA 网络揭示前列腺癌中的四个轴 ADAMTS9-AS2|MEG3/hsa-miR-150/PRKCA|MMP14。

Unveiling four axes ADAMTS9-AS2|MEG3/hsa-miR-150/PRKCA|MMP14 within prostate cancer through establishment of the ceRNA network.

机构信息

Institute of Human Genetics, Jena University Hospital, Jena, Germany.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Pathol Res Pract. 2024 Nov;263:155604. doi: 10.1016/j.prp.2024.155604. Epub 2024 Sep 25.

Abstract

Prostate cancer is among the most common cancers in males. Recent application of system biology methods has resulted in identification of key genes in the process of carcinogenesis. In the current study, we selected two datasets related to prostate cancer (PCa) and performed bulk RNA-seq analysis by selecting samples with Gleason scores greater than 7 and combining them. Subsequently, using several systems biology approaches, we constructed the ceRNA network and ultimately identified key axes related to PCa. Our analyses revealed importance of ADAMTS9-AS2/miR-150/PRKCA, ADAMTS9-AS2/miR-150/MMP14, MEG3/miR-150/PRKCA and MEG3/miR-150/MMP14 with miR-150 being a central component. Remarkably, miR-150 exhibited strong statistical significance in survival analyses. Further, analyzing expression levels from TCGA datasets, the expression of the identified genes associates significantly with prostate cancer compared to normal tissue confirming the bioinformatic analyses. Therefore, these genes can be regarded as prognostic markers in prostate cancer and the pathways are potential targets for therapeutic interventions.

摘要

前列腺癌是男性中最常见的癌症之一。最近系统生物学方法的应用已经确定了致癌过程中的关键基因。在本研究中,我们选择了两个与前列腺癌(PCa)相关的数据集,并通过选择 Gleason 评分大于 7 的样本并将其组合来进行批量 RNA-seq 分析。随后,我们使用了几种系统生物学方法,构建了 ceRNA 网络,并最终确定了与 PCa 相关的关键轴。我们的分析揭示了 ADAMTS9-AS2/miR-150/PRKCA、ADAMTS9-AS2/miR-150/MMP14、MEG3/miR-150/PRKCA 和 MEG3/miR-150/MMP14 的重要性,miR-150 是其中的核心组成部分。值得注意的是,miR-150 在生存分析中表现出很强的统计学意义。此外,通过分析 TCGA 数据集的表达水平,与正常组织相比,鉴定基因的表达与前列腺癌显著相关,证实了生物信息学分析的结果。因此,这些基因可以被视为前列腺癌的预后标志物,而这些通路是治疗干预的潜在靶点。

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