Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma.
Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma.
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DOI：
10.18632/oncotarget.8713
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发表时间：
2016-05-17
期刊：
影响因子：
--
通讯作者：
Reis PP
中科院分区：
文献类型：
--
作者：
Cinegaglia NC;Andrade SC;Tokar T;Pinheiro M;Severino FE;Oliveira RA;Hasimoto EN;Cataneo DC;Cataneo AJ;Defaveri J;Souza CP;Marques MM;Carvalho RF;Coutinho LL;Gross JL;Rogatto SR;Lam WL;Jurisica I;Reis PP
在此，我们的目的是确定整体转录组microRNA（miRNA）的变化和miRNA的靶基因在肺腺癌。选择样本作为训练集（N = 24）和独立验证集（N = 34）。显微切割组织以获得>90%的肿瘤或正常肺细胞，进行miRNA转录组测序和TaqMan定量PCR验证。我们进一步整合了我们的数据与1，491例肺腺癌和455例正常肺样本中已发表的miRNA和mRNA表达数据集。我们确定了已知的和新的，显著过度表达和表达不足的（p ≤ 0.01且FDR≤0.1）肺腺癌与正常肺组织相比的miRNA：let-7a、miR-10a、miR-15b、miR-23b、miR-26a、miR-26b、miR-29a、miR-30e、miR-99a、miR-146b、miR-181b、miR-181c、miR-421、miR-181a、miR-574和miR-1247。经验证的miRNA包括let-7a-2、let-7a-3、miR-15 b、miR-21、miR-155和miR-200 b;较高水平的miR-21表达与较低的患者存活率相关（p = 0.042）。我们确定了一个调控网络，包括miR-15 b和miR-155，以及在肺癌中具有预后价值的转录因子。我们的研究结果可能有助于肺腺癌治疗策略的发展。
Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.5
作者：
Goswami RS;Waldron L;Machado J;Cervigne NK;Xu W;Reis PP;Bailey DJ;Jurisica I;Crump MR;Kamel-Reid S
通讯作者：
Kamel-Reid S
DOI：
10.1158/1078-0432.ccr-11-2857
发表时间：
2012-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jang JS;Jeon HS;Sun Z;Aubry MC;Tang H;Park CH;Rakhshan F;Schultz DA;Kolbert CP;Lupu R;Park JY;Harris CC;Yang P;Jen J
通讯作者：
Jen J
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
4.5
作者：
Christoffersen, Nanna Ronbjerg;Silahtaroglu, Asli;Lund, Anders H.
通讯作者：
Lund, Anders H.