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

Author(s):Show less -

Cinegaglia, Naiara C. ^[1] ; Andrade, Sonia Cristina S. ^{[2, 3]} ; Tokar, Tomas ^[4] ; Pinheiro, Maisa ^[5] ; Severino, Fabio E. ^[1] ; Oliveira, Rogerio A. ^[6] ; Hasimoto, Erica N. ^[1] ; Cataneo, Daniele C. ^[1] ; Cataneo, Antonio J. M. ^[1] ; Defaveri, Julio ^[7] ; Souza, Cristiano P. ^{[8, 1]} ; Marques, Marcia M. C. ^{[8, 9]} ; Carvalho, Robson F. ^[10] ; Coutinho, Luiz L. ^[2] ; Gross, Jefferson L. ^[11] ; Rogatto, Silvia R. ^{[11, 12]} ; Lam, Wan L. ^[13] ; Jurisica, Igor ^{[14, 4, 15]} ; Reis, Patricia P. ^{[1, 16]}

Affiliation:Show less -

^[1] Sao Paulo State Univ UNESP, Dept Surg & Orthoped, Botucatu, SP - Brazil

^[2] Univ Sao Paulo, Dept Anim Biotechnol, Piracicaba, SP - Brazil

^[3] Univ Sao Paulo, Inst Biosci, BR-09500900 Sao Paulo, SP - Brazil

^[4] Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON - Canada

^[5] Sao Paulo State Univ UNESP, Dept Genet, Botucatu, SP - Brazil

^[6] Sao Paulo State Univ UNESP, Dept Biostat, Botucatu, SP - Brazil

^[7] Sao Paulo State Univ UNESP, Dept Pathol, Botucatu, SP - Brazil

^[8] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[9] Barretos Sch Hlth Sci, Barretos, SP - Brazil

^[10] Sao Paulo State Univ UNESP, Dept Morphol, Botucatu, SP - Brazil

^[11] AC Camargo Canc Ctr, Int Ctr Res & Training CIPE, Sao Paulo, SP - Brazil

^[12] UNESP, Sao Paulo State Univ, Dept Urol, Botucatu, SP - Brazil

^[13] British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC V5Z 1L3 - Canada

^[14] Univ Toronto, Dept Med Biophys, Toronto, ON - Canada

^[15] Univ Toronto, Dept Comp Sci, Toronto, ON - Canada

^[16] Sao Paulo State Univ UNESP, Expt Res Unity UNIPEX, Fac Med, Botucatu, SP - Brazil

• Document type: Journal article
• Source: ONCOTARGET; v. 7, n. 20, p. 28920-28934, MAY 17 2016.
• Web of Science Citations: 28

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. (AU)

• FAPESP's process: 11/13213-7 - Prognostic biomarkers in non-small cell lung cancer: identification of potential therapeutic targets
• Grantee: Patricia Pintor dos Reis
• Support Opportunities: Regular Research Grants