Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

Naiara C Cinegaglia; Sonia Cristina S Andrade; Tomas Tokar; Maísa Pinheiro; Fábio E Severino; Rogério A Oliveira; Erica N Hasimoto; Daniele C Cataneo; Antônio J M Cataneo; Júlio Defaveri; Cristiano P Souza; Márcia M C Marques; Robson F Carvalho; Luiz L Coutinho; Jefferson L Gross; Silvia R Rogatto; Wan L Lam; Igor Jurisica; Patricia P Reis

doi:10.18632/oncotarget.8713

Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

Naiara C Cinegaglia, Sonia Cristina S Andrade, Tomas Tokar, Maísa Pinheiro, Fábio E Severino, Rogério A Oliveira, Erica N Hasimoto, Daniele C Cataneo, Antônio J M Cataneo, Júlio Defaveri, Cristiano P Souza, Márcia M C Marques, Robson F Carvalho, Luiz L Coutinho, Jefferson L Gross, Silvia R Rogatto, Wan L Lam, Igor Jurisica, Patricia P Reis

São Paulo State University

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Oncotarget
Vol/bind	7
Udgave nummer	20
Sider (fra-til)	28920-28934
ISSN	1949-2553
DOI	https://doi.org/10.18632/oncotarget.8713
Status	Udgivet - 2016
Udgivet eksternt	Ja

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10.18632/oncotarget.8713Licens: CC BY

integrativeForlagets udgivne version, 926 KBLicens: CC BY

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Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

Citationsformater

Cinegaglia, N. C., Andrade, S. C. S., Tokar, T., Pinheiro, M., Severino, F. E., Oliveira, R. A., Hasimoto, E. N., Cataneo, D. C., Cataneo, A. J. M., Defaveri, J., Souza, C. P., Marques, M. M. C., Carvalho, R. F., Coutinho, L. L., Gross, J. L., Rogatto, S. R., Lam, W. L., Jurisica, I., & Reis, P. P. (2016). Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma. Oncotarget, 7(20), 28920-28934. https://doi.org/10.18632/oncotarget.8713

@article{2fb6658172744e5ca931a77ff09a256a,

title = "Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma",

abstract = "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.",

author = "Cinegaglia, \{Naiara C\} and Andrade, \{Sonia Cristina S\} and Tomas Tokar and Ma{\'i}sa Pinheiro and Severino, \{F{\'a}bio E\} and Oliveira, \{Rog{\'e}rio A\} and Hasimoto, \{Erica N\} and Cataneo, \{Daniele C\} and Cataneo, \{Ant{\^o}nio J M\} and J{\'u}lio Defaveri and Souza, \{Cristiano P\} and Marques, \{M{\'a}rcia M C\} and Carvalho, \{Robson F\} and Coutinho, \{Luiz L\} and Gross, \{Jefferson L\} and Rogatto, \{Silvia R\} and Lam, \{Wan L\} and Igor Jurisica and Reis, \{Patricia P\}",

year = "2016",

doi = "10.18632/oncotarget.8713",

language = "English",

volume = "7",

pages = "28920--28934",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals LLC",

number = "20",

}

Cinegaglia, NC, Andrade, SCS, Tokar, T, Pinheiro, M, Severino, FE, Oliveira, RA, Hasimoto, EN, Cataneo, DC, Cataneo, AJM, Defaveri, J, Souza, CP, Marques, MMC, Carvalho, RF, Coutinho, LL, Gross, JL, Rogatto, SR, Lam, WL, Jurisica, I & Reis, PP 2016, 'Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma', Oncotarget, bind 7, nr. 20, s. 28920-28934. https://doi.org/10.18632/oncotarget.8713

TY - JOUR

T1 - Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

AU - Cinegaglia, Naiara C

AU - Andrade, Sonia Cristina S

AU - Tokar, Tomas

AU - Pinheiro, Maísa

AU - Severino, Fábio E

AU - Oliveira, Rogério A

AU - Hasimoto, Erica N

AU - Cataneo, Daniele C

AU - Cataneo, Antônio J M

AU - Defaveri, Júlio

AU - Souza, Cristiano P

AU - Marques, Márcia M C

AU - Carvalho, Robson F

AU - Coutinho, Luiz L

AU - Gross, Jefferson L

AU - Rogatto, Silvia R

AU - Lam, Wan L

AU - Jurisica, Igor

AU - Reis, Patricia P

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.18632/oncotarget.8713

DO - 10.18632/oncotarget.8713

M3 - Journal article

C2 - 27081085

SN - 1949-2553

VL - 7

SP - 28920

EP - 28934

JO - Oncotarget

JF - Oncotarget

IS - 20

ER -

Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

Abstract

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