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对保护性miRNA进行查,并构建新的lncRNA/miRNA/mRNA网络和预后模型,用于三阴性乳腺癌

Yuelei Zhao¹, Yichen Song¹, Yan Zhang¹

¹Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, PR China.

Molecular and cellular probes

|October 23, 2023

概括

研究人员发现,与其他乳腺癌相比,微RNA (miRNA) 在三阴性乳腺癌 (TNBC) 中具有相反的生存关联. 他们开发了一种用于TNBC预后的3miRNA模型,将IRS-1确定为关键目标基因.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

三重阴性乳腺癌 (TNBC) 的预后不好,缺乏向治疗.
微RNAs (miRNAs) 参与TNBC进展,但它们的表达和功能是异质的.
识别新的分子标对于改善TNBC预后和治疗至关重要.

研究的目的:

分析TNBC中的miRNA表达模式,并确定预后生物标志物.
开发TNBC患者整体生存预测模型.
阐明涉及miRNAs,lncRNAs和mRNAs在TNBC中的调节网络.

主要方法:

来自癌症基因组图谱 (TCGA) 的miRNA表达数据的分析.
应用单变量和多变量考克斯比例危险回归模型.
使用转录组数据构建一个lncRNA-miRNA-mRNA调节网络.
在体外验证miRNA-目标相互作用和功能测试.

主要成果:

过度表达的miRNA与TNBC的更好的生存率有关,与其他乳腺癌形成鲜明对比.
一个3-miRNA预后模型显示AUC为0.727用于预测TNBC总生存期.
IRS-1被确定为一个顶部枢纽基因,由miR-15b-5p和miR-148a-3p作为目标.
miR-148a-3p显著抑制了TNBC细胞迁移和活力.

结论:

识别的3-miRNA模型为TNBC风险评估和临床应用提供了强大的工具.
这项研究揭示了对TNBC异质miRNA景观的新见解.
准特定的miRNA及其下游通路,如IRS-1,有可能为TNBC特异性疗法提供潜力.

关键词:

乳腺癌乳腺癌乳腺癌预测模型是一个预测模型.在TCGA中,TCGA就是TCGA.在ncRNAs/miRNAs/mRNAs网络中.这就是miRNAs.

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lncRNA - Long Non-coding RNAs

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...