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Title:	YKT6 expression, exosome release, and survival in non-small cell lung cancer
Author:	Ruíz Martínez, Marc; Navarro Ponz, Alfons; Marrades Sicart, Ramon Ma.; Viñolas Segarra, Núria; Santasusagna, Sandra; Muñoz García, Carmen; Ramírez Ruz, J. (José); Molins López-Rodó, Laureano; Monzó Planella, Mariano
Notes:	BACKGROUND: Cancer-derived exosomes are involved in metastasis. YKT6 is a SNARE protein that participates in the regulation of exosome production and release, but its role in non-small cell lung cancer (NSCLC) has not been examined. MATERIALS AND METHODS: Ultracentrifugation-purified exosomes from the A549 cell line were studied by CRYO-TEM, nanoparticle tracking analysis and western blot (TSG101 marker). YKT6 was inhibited using a DsiRNA and selected pre-microRNAs. MicroRNAs targeting YKT6 were validated by Renilla/Luciferase assay and western blot. YKT6 expression and its prognostic impact were analyzed in 98 tissue specimens from resected NSCLC patients. RESULTS: Membranous nanosized vesicles (mode size: 128nm) with TSG101 protein were purified from A549 cells. YKT6 inhibition reduced exosome release by 80.9%. We validated miR-134 and miR-135b as miRNAs targeting YKT6, and transfection with the pre-miRNAs also produced a significant reduction in exosome release. The analysis of YKT6 in tumor samples showed that patients with high levels had shorter disease-free and overall survival. CONCLUSIONS: YKT6 is a key molecule in the regulation of exosome release in lung cancer cells and is in turn precisely regulated by miR-134 and miR-135b. Moreover, YKT6 levels impact prognosis of resected NSCLC patients.
Subject(s):	-Càncer de pulmó -Proteïnes citosquelètiques -Micro RNAs -Lung cancer -Cytoskeletal proteins -MicroRNAs
Rights:	cc-by (c) Ruíz Martínez, Marc et al., 2016 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Impact Journals
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