Integrative analysis of lncRNAs and miRNAs with coding RNAs associated with ceRNA crosstalk network in triple negative breast cancer.
Integrative analysis of lncRNAs and miRNAs with coding RNAs associated with ceRNA crosstalk network in triple negative breast cancer.
复制标题
三阴性乳腺癌中 lncRNA 和 miRNA 以及与 ceRNA 串扰网络相关的编码 RNA 的综合分析
DOI：
10.2147/ott.s149308
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发表时间：
2017
影响因子：
4
通讯作者：
Hao X
中科院分区：
文献类型：
--
作者：
Yuan N;Zhang G;Bie F;Ma M;Ma Y;Jiang X;Wang Y;Hao X
三阴性乳腺癌（Triple Negative Breast Cancer，TNBC）是乳腺恶性肿瘤的一种特殊亚型，其预后比其他分子亚型差。目前，人们越来越关注长链非编码RNA（lncRNA），其可以充当竞争性内源RNA（ceR-NAs）并抑制参与肿瘤中转录后调控网络的miRNA功能。因此，为了研究TNBC致癌的具体机制并提高治疗效率，我们全面整合了表达谱，包括来自癌症基因组图谱的116个TNBC组织和11个正常组织的mRNA、lncRNA和miRNA数据。因此，我们选择了阈值，|log 2光纤通道|05，以获得差异表达的mRNA、miRNA和lncRNA。随后，进行加权基因共表达网络分析，以确定失调基因的表达特征。我们获得了5个共表达模块及相关临床特征。通过基因模块关联和蛋白质相互作用网络分析，筛选出22个可以作为中枢靶基因的hub mRNAs。11个关键的失调差异表达的微小RNA（DEmiRNAs）被确定为与22个枢纽潜在的靶基因显着相关。此外，我们发现14个关键的差异表达lncRNA可以与关键的DEmiRNAs相互作用。然后，通过在Cytoscape软件中利用关键lncRNA、关键miRNA和枢纽mRNA构建TNBC的ceRNA串扰网络。我们分析和描述了TNBC ceRNA共调控网络的生物学功能和病理学作用的潜在特征;还对每个分子进行了存活分析。这些发现揭示了ceRNA串扰网络可能在TNBC的发生和进展中发挥重要作用。此外，我们还确定了ceRNA网络中的一些分子具有临床相关性和预后。
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 p-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.