重构长非编码RNA介导的乳腺癌basal-like亚型相关药物互作网络

Reconstructing breast cancer basal-like subtype-related drugs network mediated by long non-coding RNA

目的基于长非编码RNA(lncRNA)及mRNA双重表达谱,构建乳腺癌basal-like亚型相关的lncRNA-mRNA-drug互作网络。方法以乳腺癌basal-like亚型为疾病模型,基于新一代测序技术构建乳腺癌长非编码RNA与编码RNA转录组分子图谱,采用关联有罪的原理识别了basal-like亚型中显著差异改变的lncRNA-mRNA共表达对,进而结合药物及其靶关系构建lncRNA-mRNA-drug互作网络。结果基于RNA-seq数据获得的双重表达谱共识别了1 122个差异表达的lncRNA和6 370个差异表达的mRNA,利用DAVID识别了显著富集的29个生物学功能及8条KEGG通路,最终结合药物及其靶关系构建了非编码RNA介导的乳腺癌亚型相关的药物互作网络。结论基于TCGA的lncRNA及mRNA双重表达谱,从计算系统生物学角度提出了识别乳腺癌basal-like亚型相关风险lncRNA新策略,构建了非编码RNA介导的乳腺癌basal-like亚型相关药物互作网络,为解析乳腺癌basal-like亚型分子机制及药物重定位提供了重要的科学依据。

Objective To reconstruct the specific lncRNA-mRNA-drug interaction network in breast cancer basal-like subtype based on the expression profiles of long non-coding RNAs ( lncRNAs) and mRNAs,which provided an important scientific reference for further exploring the pathogenesis and precise treatment of breast cancer. Methods The basal-like subtype of breast cancer was used as a disease model to construct a molecular map of long non-coding RNA and mRNA of breast cancer based on next-generation sequencing technology. The association of guilty was used to identify significant differences in basal-like subtypes. A lncRNA-mR- NA-drug interaction network was constructed by the lncRNA-mRNA co-expression pair,in combination with the drug and its target relationship. Results Based on RNA-seq data,the dual expression profiles which identified 1 122 differentially expressed lncRNAs and 6 370 differentially expressed mRNAs were obtained. Twenty nine enriched biological functions and 8 KEGG pathways were identified by DAVID,and finally a non-coding RNA-mediated drug interaction network associated with breast cancer subtypes was constructed by combination of the drugs and its target relationship. Conclusion Based on the dual expression profiles of lncRNA and mRNA of TCGA,a novel strategy for identifying lncRNAs of basal-like subtypes in breast cancer was proposed based on the computational systems biology,and the long non-coding RNA-mediated drug interaction network of basal-like subtype in breast cancer was constructed, which provided an important scientific basis for the analysis of the molecular mechanism and drug relocation of basal-like subtypes in breast cancer.