Počet záznamů: 1
MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma
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SYSNO ASEP 0465816 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma Tvůrce(i) Tomasetti, M. (IT)
Monaco, F. (IT)
Manzella, N. (IT)
Rohlena, Jakub (BTO-N) RID, ORCID
Rohlenová, Kateřina (BTO-N) ORCID, RID
Staffolani, S. (IT)
Gaetani, S. (IT)
Ciarapica, V. (IT)
Amati, M. (IT)
Bracci, M. (IT)
Valentino, M. (IT)
Goodwin, J. (IT)
Nguyen, M. (AU)
Truksa, Jaroslav (BTO-N) RID, ORCID
Sobol, Margaryta (UMG-J) RID
Hozák, Pavel (UMG-J) RID, ORCID
Dong, L.F. (AU)
Santarelli, L. (IT)
Neužil, Jiří (BTO-N) RIDCelkový počet autorů 19 Zdroj.dok. OncoTarget. - : Impact Journals LLC - ISSN 1949-2553
Roč. 7, č. 24 (2016), s. 36338-36352Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova pyruvate-dehydrogenase kinase ; mir-126 ; angiogenesis ; tumor suppression Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP301/10/1937 GA ČR - Grantová agentura ČR LM2015062 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy TE01020118 GA TA ČR - Technologická agentura ČR GA16-22823S GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000377756800066 DOI 10.18632/oncotarget.8916 Anotace Autophagy favors both cell survival and cancer suppression, and increasing evidence reveals that microRNAs (MIRs) regulate autophagy. Previously we reported that MIR126 is downregulated in malignant mesothelioma (MM). Therefore, we investigated the role of MIR126 in the regulation of cell metabolism and autophagy in MM models. We report that MIR126 induces autophagic flux in MM cells by downregulating insulin receptor substrate-1 (IRS1) and disrupting the IRS1 signaling pathway. This was specific to MM cells, and was not observed in non-malignant cells of mesothelial origin or in MM cells expressing MIR126-insensitive IRS1 transcript. The MIR126 effect on autophagy in MM cells was recapitulated by IRS1 silencing, and antagonized by IRS1 overexpression or antisense MIR126 treatment. The MIR126-induced loss of IRS1 suppressed glucose uptake, leading to energy deprivation and AMPK-dependent phosphorylation of ULK1. In addition, MIR126 stimulated lipid droplet accumulation in a hypoxia-inducible factor-1 alpha (HIF1 alpha)-dependent manner. MIR126 also reduced pyruvate dehydrogenase kinase (PDK) and acetyl-CoA-citrate lyase (ACL) expression, leading to the accumulation of cytosolic citrate and paradoxical inhibition of pyruvate dehydrogenase (PDH) activity. Simultaneous pharmacological and genetic intervention with PDK and ACL activity phenocopied the effects of MIR126. This suggests that in MM MIR126 initiates a metabolic program leading to high autophagic flux and HIF1 alpha stabilization, incompatible with tumor progression of MM. Consistently, MIR126-expressing MM cells injected into immunocompromised mice failed to progress beyond the initial stage of tumor formation, showing that increased autophagy has a protective role in MM. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2017
Počet záznamů: 1