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

• Grant number: 16/06381-4
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: July 01, 2016
• End date: December 31, 2016
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Patricia Pintor dos Reis
• Grantee: Patricia Pintor dos Reis
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

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 macrodissected 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 adenocarcinomas and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (pd0.01 and FDRd0.1) 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)