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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
Keywords: Càncer de pulmó
Proteïnes citosquelètiques
Micro RNAs
Lung cancer
Cytoskeletal proteins
Issue Date: 6-Jun-2016
Publisher: Impact Journals
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2016, vol. 7, num. 32, p. 51515-51524
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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