Integral Analyses of Competing Endogenous RNA Mechanisms and DNA Methylation Reveal Regulatory Mechanisms in Osteosarcoma.
Integral Analyses of Competing Endogenous RNA Mechanisms and DNA Methylation Reveal Regulatory Mechanisms in Osteosarcoma.
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DOI：
10.3389/fcell.2021.763347
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发表时间：
2021
影响因子：
5.5
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Wu T;Wei B;Lin H;Zhou B;Lin T;Liu Q;Sang H;Liu H;Huang W
背景：骨肉瘤(Osteosaroma，OS)是儿童青少年最常见的原发恶性骨肿瘤，生长快、转移频繁、预后差，其发病机制尚未完全阐明。探讨OS的发病机制对提高诊断水平和寻找新的治疗靶点具有重要意义。方法：鉴定OS细胞和对照细胞之间差异表达的CircRNAs(DECs)、miRNAs(Dem)、甲基化DNA位点(DMS)和mRNAs(Degs)。进行了DEGS的GSEA和甲基化DEGS的功能富集化分析，以进一步确定潜在的生物学过程。利用在线工具预测DECS的miRNA结合位点和DEM的mRNA结合位点，构建CircRNA-miRNA-mRNA网络。然后，用蛋白质-蛋白质相互作用(PPI)网络分析甲基化DEG之间的相互作用，并进行HUB基因鉴定和生存分析。用实时荧光定量聚合酶链式反应验证CircRNA-miRNA-mRNAm RNA的表达模式。结果：GSEA和功能富集度分析表明DEGS和甲基化DEGS参与了肿瘤的重要生物学过程。构建了HSA_CIRC_0001753/HAS_miR_760/CD74网络，并在细胞株中进行了验证。CD74表达水平低与总生存时间短相关，表现出良好的诊断能力。结论：DGS甲基化可能参与了OS的发生发展，hSA_CIRC_0001753/HAS_miR_760/CD74网络可作为OS的早期诊断和靶向治疗的靶点。
Background: Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents, with rapid growth, frequent metastasis, and a poor prognosis, but its pathogenesis has not been fully elucidated. Exploring the pathogenesis of OS is of great significance for improving diagnoses and finding new therapeutic targets. Methods: Differentially expressed circRNAs (DECs), miRNAs (DEMs), methylated DNA sites (DMSs), and mRNAs (DEGs) were identified between OS and control cell lines. GSEA of DEGs and functional enrichment analysis of methylated DEGs were carried out to further identify potential biological processes. Online tools were used to predict the miRNA binding sites of DECs and the mRNA binding sites of DEMs, and then construct a circRNA-miRNA-mRNA network. Next, an analysis of the interaction between methylated DEGs was performed with a protein-protein interaction (PPI) network, and hub gene identification and survival analysis were carried out. The expression pattern of circRNA-miRNA-mRNA was validated by real-time PCR. Results: GSEA and functional enrichment analysis indicated that DEGs and methylated DEGs are involved in important biological processes in cancer. Hsa_circ_0001753/has_miR_760/CD74 network was constructed and validated in cell lines. Low expression levels of CD74 are associated with poor overall survival times and show good diagnostic ability. Conclusion: Methylated DEGs may be involved in the development of OS, and the hsa_circ_0001753/has_miR_760/CD74 network may serve as a target for the early diagnosis of and targeted therapy for OS.
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