Li D-S, Ainiwaer J-L, Sheyhiding I, Zhang Z, Zhang L-W
Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of
Eur Rev Med Pharmacol Sci. 2016 Jun;20(11):2285-95.
RNA-seq data and miRNA-seq data of lung adenocarcinoma (LUAD) were analyzed to identify critical long non-coding RNAs (lncRNAs) and disclose molecular pathogenesis.
RNA-seq data and miRNA-seq data were downloaded from TCGA. Differentially expressed lncRNAs (DELs) and microRNAs (DEMs) were revealed by two sample t-test. |Fold change| > 2 and p-value < 0.01 were set as the cutoffs. Univariate Cox regression was performed to disclose prognostic lncRNAs. Information about miRNA-lncRNA interactions and miRNA-mRNA interactions were acquired from miRcode and miRTarBase, respectively. A miRNA-lncRNA-mRNA regulatory network was then constructed, from which regulatory modules were identified. Functional enrichment analysis was performed with DAVID.
A total of 57 DELs and 118 DEMs were identified from 507 LUAD compared with 19 normal samples. Three DELs, including MEG3, MIAT and MIR4697HG, were associated with clinical features, while nine DELs (LINC00115, LINC00265, LINC01001, LINC01002, MIR22HG, NFYC-AS1, SNHG10, THUMPD3-AS1 and TMPO-AS1) were revealed to be prognostic biomarkers. A regulatory network including 61 miRNA-lncRNA interactions and 304 miRNA-mRNA interactions was constructed, from which 19 lncRNA-miRNA-mRNA regulatory modules were identified. Among the modules, MEG3 and MIAT may play important roles in the development of LUAD by interactions with miR-106 which then regulated the MAPK9 to involve in MAPK signaling pathways. LINC00115 might interact with miR-7 to regulate FGF2 to participate in pathways in cancer.
MEG3, MIAT, LINC00115 may be underlying therapeutic targets for LUAD functioning as ceRNAs for regulation of miRNA-mRNA.
分析肺腺癌（LUAD）的RNA测序数据和微小RNA测序数据，以鉴定关键的长链非编码RNA（lncRNA）并揭示分子发病机制。
从TCGA下载RNA测序数据和微小RNA测序数据。通过两样本t检验揭示差异表达的lncRNA（DEL）和微小RNA（DEM）。将|倍数变化|>2且p值<0.01设定为截断值。进行单因素Cox回归以揭示预后lncRNA。分别从miRcode和miRTarBase获取有关微小RNA-lncRNA相互作用和微小RNA-mRNA相互作用的信息。然后构建微小RNA-lncRNA-mRNA调控网络，从中识别调控模块。使用DAVID进行功能富集分析。
与19个正常样本相比，从507例LUAD中鉴定出总共57个DEL和118个DEM。包括MEG3、MIAT和MIR4697HG在内的3个DEL与临床特征相关，而9个DEL（LINC00115、LINC00265、LINC01001、LINC01002、MIR22HG、NFYC-AS1、SNHG10、THUMPD3-AS1和TMPO-AS1）被揭示为预后生物标志物。构建了一个包含61个微小RNA-lncRNA相互作用和304个微小RNA-mRNA相互作用的调控网络，从中识别出19个lncRNA-微小RNA-mRNA调控模块。在这些模块中，MEG3和MIAT可能通过与miR-106相互作用在LUAD的发展中发挥重要作用，miR-106随后调节MAPK9以参与MAPK信号通路。LINC00115可能与miR-7相互作用以调节FGF2参与癌症相关通路。
MEG3、MIAT、LINC00115可能是LUAD潜在的治疗靶点，作为竞争性内源RNA调节微小RNA-mRNA。
