Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma
| Autor: | Jefferson L Gross, Naiara Cinegaglia, Antonio José Maria Cataneo, Julio Defaveri, Sónia C. S. Andrade, Luiz Lehmann Coutinho, Erica Nishida Hasimoto, Robson Francisco Carvalho, Igor Jurisica, Rogério Antonio de Oliveira, Daniele Cristina Cataneo, Cristiano de Pádua Souza, Wan L. Lam, Fabio E. Severino, Márcia Martins Marques, Silvia Regina Rogatto, Maisa Pinheiro, Patricia P Reis, Tomas Tokar |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Lung Neoplasms molecular targets Adenocarcinoma of Lung transcription factor networks Kaplan-Meier Estimate transcriptome sequencing Adenocarcinoma Transcriptome 03 medical and health sciences 0302 clinical medicine microRNA medicine TaqMan Humans Gene Regulatory Networks Lung cancer Aged Aged 80 and over Lung business.industry Gene Expression Profiling Middle Aged medicine.disease lung adenocarcinoma microRNAs Gene expression profiling 030104 developmental biology medicine.anatomical_structure Real-time polymerase chain reaction Oncology 030220 oncology & carcinogenesis Cancer research Female business Research Paper Transcription Factors |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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