筛选保护性miRNAs并构建新的lncRNAs/miRNAs/mRNA网络和癌症三阴性预后模型。

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Yuelei Zhao , Yichen Song , Yan Zhang , Meiju Ji , Peng Hou , Fang Sui
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引用次数: 0

摘要

癌症三阴性(TNBC)代表10-20 % 在所有癌症(BC)病例中,以预后不良为特征。鉴于迫切需要改善TNBC的预后和开发特异性疗法,识别新的分子靶点具有重要意义。微小RNA(miRNA)已被报道为TNBC进展中一种有价值的新分子靶点。然而,miRNA在不同肿瘤中的表达和功能是异质的。在此,我们首先分析了来自癌症基因组图谱(TCGA)的miRNA数据,并惊奇地发现,在所有癌症患者中,过表达的miRNA与较差的生存率相关,但在TNBC患者中,过度表达的miRNAs与较好的生存率有关。基于TNBC中miRNA表达的异质性,我们使用单变量Cox比例风险回归模型进行了进一步分析,并确定了17种具有预后潜力的miRNA。随后,采用多变量Cox模型创建3-miRNA预后模型,用于预测TNBC患者的总生存率。诊断模型的曲线下面积(AUC)为0.727,多变量Cox回归表明每个协变量都与生存率相关。这些数据表明,该模型对风险评估相对准确、稳健,具有一定的临床应用价值。为了探索TNBC中过表达miRNA背后的网络,我们通过TCGA数据库中匹配样本的完整转录组数据,建立了一个由lncRNA、miRNA和mRNA组成的新网络。在这个网络中,IRS-1似乎是最重要的枢纽基因。实验结果表明,miR-15b-5p和miR-148a-3p在体外有效靶向IRS-1,揭示了异质性miRNA介导的TNBC的复杂调控机制。此外,miR-148a-3p显著抑制细胞迁移和活力。总的来说,这项研究可能会为基于miRNA的TNBC的分子格局提供有价值的见解,并有可能为TNBC的靶向治疗和改善预后策略的发展做出贡献。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Screening protective miRNAs and constructing novel lncRNAs/miRNAs/mRNAs networks and prognostic models for triple-negative breast cancer

Triple-negative breast cancer (TNBC) represents 10–20 % of all breast cancer (BC) cases and is characterized by poor prognosis. Given the urgent need to improve prognostication and develop specific therapies for TNBC, the identification of new molecular targets is of great importance. MicroRNA (miRNA) has been reported as a valuable and novel molecular target in the progression of TNBC. However, the expression and function of miRNAs in different tumors are heterogeneous. Herein, we first analyzed miRNA data from The Cancer Genome Atlas (TCGA) and surprisedly found that overexpressed miRNAs were associated with poor survival in all breast cancer patients, but the overexpressed miRNAs were associated with better survival in TNBC patients. Based on the heterogeneity of miRNA expression in TNBC, we conducted further analysis using univariate Cox proportional hazard regression models and identified 17 miRNAs with prognostic potential. Subsequently, a multivariate Cox model was employed to create a 3-miRNA prognostic model for predicting overall survival in TNBC patients. The diagnostic model exhibited an area under the curve (AUC) of 0.727, and multivariable Cox regression indicated that each covariate was associated with survival. These data indicate that this model is relatively accurate and robust for risk assessment, which have a certain value for clinical application. In order to explore the network behind the overexpressed miRNAs in TNBC, we established a novel network consisting of lncRNAs, miRNAs, and mRNAs through complete transcriptome data from matched samples in the TCGA database. In this network, IRS-1 appeared to be the top hub gene. Experimental results demonstrated that miR-15b-5p and miR-148a-3p effectively target IRS-1 in vitro, shedding light on the intricate regulatory mechanisms in TNBC mediated by the heterogeneous miRNAs. Besides, miR-148a-3p significantly inhibited cell migration and viability. Overall, this study may add valuable insights into the molecular landscape of TNBC based on miRNAs and have the potential to contribute to the development of targeted therapies and improved prognostic strategies of TNBC.

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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
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