MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD

Molina-Pinelo, Sonia et al.Lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that share common aetiological factors (tobacco smoking) and probable dysregulated pathways. MicroRNAs (miRNAs) play an essential role in regulating numerous physiological and pathological processes. The purpose of this study was to assess global miRNA expression patterns in patients with COPD and/or adenocarcinoma to elucidate distinct regulatory networks involved in the pathogenesis of these two smoking-related diseases. Expression of 381 miRNAs was quantified by TaqMan Human MicroRNA A Array v2.0 in bronchoalveolar lavage fluid samples from 87 patients classified into four groups: COPD, adenocarcinoma, adenocarcinoma with COPD, and control (neither COPD nor adenocarcinoma). 11 differentially expressed miRNAs were randomly selected for validation in an independent cohort of 40 patients. Distinct miRNA expression profiles were identified and validated for each pathological group, involving 66 differentially expressed miRNAs. Four miRNA clusters (the mir-17-92 cluster and its paralogues, mir-106a-363 and mir-106b-25; and the miR-192-194 cluster) were upregulated in patients with adenocarcinoma and one miRNA cluster (miR-132-212) was upregulated in patients with COPD. These results contribute to unravelling miRNA-controlled networks involved in the pathogenesis of adenocarcinoma and COPD, and provide new tools of potential use as biomarkers for diagnosis and/or therapeutic purposes.L. Paz-Ares is funded by Fondo de Investigación Sanitaria (PI1102688) and RTICC (R12/0036/0028). S. Molina-Pinelo is funded by Fondo de Investigación Sanitaria (CD1100153), Fundación Científica de la Asociación Española Contra el Cáncer, Consejería de Salud y Bienestar Social PI-0046-2012 and Fundación Mutua Madrileña (2010). M.D. Pastor is funded by Fondo de Investigación Sanitaria (CD0900148). The A. Carnero laboratory was supported by grants to from the Spanish Ministry of Economy and Competitivity, ISCIII (PI12/00137, RTICC: RD12/0036/0028), Consejeria de Ciencia e Innovacion (CTS-6844) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012).Peer Reviewe