title: MicroRNA-dependent regulation of transcription in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Molina-Pinelo
authors.affiliation: Genetic Department, Universidad de Sevilla, Seville, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gutiérrez
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Pastor
authors.affiliation: Biochemistry Department, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas 'Alberto Sols' CSIC-UAM, Madrid, Spain; IdiPAZ (Instituto de Investigación Sanitaria La Paz) & Fundación MD Anderson International, Madrid Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Hergueta
authors.affiliation: Biochemistry Department, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas 'Alberto Sols' CSIC-UAM, Madrid, Spain; IdiPAZ (Instituto de Investigación Sanitaria La Paz) & Fundación MD Anderson International, Madrid Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain; Medical Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Carbonero
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Nogal
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Suárez
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Salinas
authors.affiliation: Service of Neumology, Hospital 12 de Octubre, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Pozo-Rodríguez
authors.affiliation: Pathology Department, Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico Clara Campal, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopez-Rios
authors.affiliation: Service of Oncology, Instituto de Investigación Sanitaria i+12, Hospital Doce de Octubre, Madrid, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Agulló-Ortuño
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Service of Neumology, Hospital Severo Ochoa, Madrid, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Perpiñá
authors.affiliation: Department of Pathology, Hospital Universitario Ramón y Cajal, Instituto de Investigación Sanitaria Ramón y Cajal (IRYCIS), Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Palacios
authors.affiliation: Molecular Biology of Cancer Group, Instituto de Biomedicina de Sevilla (IBIS)/(HUVR, CSIC, Universidad de Sevilla), Seville, Spain.
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.affiliation: Molecular Oncology and New Therapies Group. Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain; Medical Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D035683:MicroRNAs