MicroRNA-dependent regulation of transcription in non-small cell lung cancer

Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgr...

Descripción completa

Detalles Bibliográficos
Autores: Molina-Pinelo, Sonia, Gutiérrez, Gabriel M., Pastor, María Dolores, Hergueta, Marta, Moreno Bueno, Gema, García Carbonero, Rocío, Nogal, Ana, Suárez, Rocío, Salinas, Ana María, Pozo-Rodríguez, Francisco, López-Ríos, Fernando, Agulló-Ortuño, María Teresa, Ferrer, Irene, Perpiñá, Asunción, Palacios, José Luis, Carnero, Amancio, Paz-Ares, Luís G.
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/665035
Acceso en línea:http://hdl.handle.net/10486/665035
https://dx.doi.org/10.1371/journal.pone.0090524
Access Level:acceso abierto
Palabra clave:gene expression
histology
lung non small cell cancer
microarray analysis
RNA analysis
Medicina
Descripción
Sumario:Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies