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基于生物信息学分析鉴定预测骨肉瘤进展的候选 microRNA-mRNA 子网络。

Identification of Candidate MicroRNA-mRNA Subnetwork for Predicting the Osteosarcoma Progression by Bioinformatics Analysis.

机构信息

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning 530021, China.

出版信息

Comput Math Methods Med. 2022 Sep 22;2022:1821233. doi: 10.1155/2022/1821233. eCollection 2022.

Abstract

Osteosarcoma (OS) is the pretty common primary cancer of the bone among the malignancies in adolescents. A single molecular component or a limited number of molecules is insufficient as a predictive biomarker of OS progression. Hence, it is necessary to find novel network biomarkers to improve the prediction and therapeutic effect for OS. Here, we identified 230 DE-miRNAs and 821 DE-mRNAs through two miRNA expression-profiling datasets and three mRNA expression-profiling datasets. We found that hsa-miR-494 is closely linked with the survival of OS patients. In addition, we analyzed GO and KEGG enrichment for targets of hsa-miR-494-5p and hsa-miR-494-3p through R programming. And five mRNAs were predicted as common targets of hsa-miR-494-5p and hsa-miR-494-3p. We further revealed that upregulated TRPS1 was strongly correlated with poor outcomes in OS patients through the survival analysis based on the TARGET database. The qRT-PCR study verified that the expression of hsa-miR-494-5p and hsa-miR-494-3p was declined considerably, while TRPS1 was notably raised in OS cells when compared to the osteoblasts. Thus, we generated a new regulatory subnetwork of key miRNAs and target mRNAs using Cytoscape software. These results indicate that the novel miRNA-mRNA subnetwork composed of hsa-miR-494-5p, hsa-miR-494-3p, and TRPS1 might be a characteristic molecule for assessing the prognostic value of OS patients.

摘要

骨肉瘤(OS)是青少年恶性肿瘤中常见的原发性骨癌。单一的分子成分或少数分子不足以作为 OS 进展的预测性生物标志物。因此,有必要寻找新的网络生物标志物,以提高 OS 的预测和治疗效果。在这里,我们通过两个 miRNA 表达谱数据集和三个 mRNA 表达谱数据集鉴定了 230 个 DE-miRNA 和 821 个 DE-mRNA。我们发现 hsa-miR-494 与 OS 患者的生存密切相关。此外,我们通过 R 编程分析了 hsa-miR-494-5p 和 hsa-miR-494-3p 靶基因的 GO 和 KEGG 富集。预测了 5 个 mRNAs 是 hsa-miR-494-5p 和 hsa-miR-494-3p 的共同靶基因。我们进一步通过 TARGET 数据库的生存分析发现,上调的 TRPS1 与 OS 患者的不良预后密切相关。qRT-PCR 研究验证了与成骨细胞相比,OS 细胞中 hsa-miR-494-5p 和 hsa-miR-494-3p 的表达明显下调,而 TRPS1 的表达明显上调。因此,我们使用 Cytoscape 软件生成了一个由 hsa-miR-494-5p、hsa-miR-494-3p 和 TRPS1 组成的新的关键 miRNA 和靶 mRNA 调控子网络。这些结果表明,由 hsa-miR-494-5p、hsa-miR-494-3p 和 TRPS1 组成的新 miRNA-mRNA 子网络可能是评估 OS 患者预后价值的特征分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5c/9553349/aab6e377102d/CMMM2022-1821233.001.jpg

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