Yuan Naijun, Zhang Guijuan, Bie Fengjie, Ma Min, Ma Yi, Jiang Xuefeng, Wang Yurong, Hao Xiaoqian
College of Traditional Chinese Medicine of Jinan University, Institute of Integrated Traditional Chinese and Western Medicine of Jinan University.
The First Affiliated Hospital of Jinan University.
Onco Targets Ther. 2017 Dec 12;10:5883-5897. doi: 10.2147/OTT.S149308. eCollection 2017.
Triple negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Currently, there is increasing focus on long non-coding RNAs (lncRNAs), which can act as competing endogenous RNAs (ceR-NAs) and suppress miRNA functions involved in post-transcriptional regulatory networks in the tumor. Therefore, to investigate specific mechanisms of TNBC carcinogenesis and improve treatment efficiency, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 116 TNBC tissues and 11 normal tissues from The Cancer Genome Atlas. As a result, we selected the threshold with |log2FC|>2.0 and an adjusted -value >0.05 to obtain the differentially expressed mRNAs, miRNAs and lncRNAs. Hereafter, weighted gene co-expression network analysis was performed to identify the expression characteristics of dysregulated genes. We obtained five co-expression modules and related clinical feature. By means of correlating gene modules with protein-protein interaction network analysis that had identified 22 hub mRNAs which could as hub target genes. Eleven key dysregulated differentially expressed micro RNAs (DEmiRNAs) were identified that were significantly associated with the 22 hub potential target genes. Moreover, we found that 14 key differentially expressed lncRNAs could interact with the key DEmiRNAs. Then, the ceRNA crosstalk network of TNBC was constructed by utilizing key lncRNAs, key miRNAs, and hub mRNAs in Cytoscape software. We analyzed and described the potential characteristics of biological function and pathological roles of the TNBC ceRNA co-regulatory network; also, the survival analysis was performed for each molecule. These findings revealed that ceRNA crosstalk network could play an important role in the development and progression for TNBC. In addition, we also identified that some molecules in the ceRNA network possess clinical correlation and prognosis.
三阴性乳腺癌(TNBC)是一种特殊的乳腺恶性肿瘤亚型,其预后比其他分子亚型更差。目前,人们越来越关注长链非编码RNA(lncRNA),它可以作为竞争性内源性RNA(ceRNA),抑制肿瘤转录后调控网络中涉及的miRNA功能。因此,为了研究TNBC致癌的具体机制并提高治疗效率,我们综合整合了表达谱,包括从癌症基因组图谱中获取的116个TNBC组织和11个正常组织的mRNA、lncRNA和miRNA数据。结果,我们选择|log2FC|>2.0且校正后P值>0.05的阈值来获得差异表达的mRNA、miRNA和lncRNA。此后,进行加权基因共表达网络分析以识别失调基因的表达特征。我们获得了五个共表达模块和相关临床特征。通过将基因模块与蛋白质-蛋白质相互作用网络分析相关联,确定了22个可能作为枢纽靶基因的枢纽mRNA。鉴定出11个关键失调的差异表达微小RNA(DEmiRNA),它们与22个枢纽潜在靶基因显著相关。此外,我们发现14个关键差异表达的lncRNA可以与关键DEmiRNA相互作用。然后,利用关键lncRNA、关键miRNA和枢纽mRNA在Cytoscape软件中构建了TNBC的ceRNA串扰网络。我们分析并描述了TNBC ceRNA共调控网络的潜在生物学功能特征和病理作用;此外,还对每个分子进行了生存分析。这些发现表明,ceRNA串扰网络可能在TNBC的发生和发展中发挥重要作用。此外,我们还确定ceRNA网络中的一些分子具有临床相关性和预后价值。