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Evidence of novel miR-34a-based therapeutic approaches for multiple myeloma treatment

MR. Zarone, G. Misso, A. Grimaldi, S. Zappavigna, M. Russo, E. Amler, MT. Di Martino, N. Amodio, P. Tagliaferri, P. Tassone, M. Caraglia,

. 2017 ; 7 (1) : 17949. [pub] 20171220

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19035468

MiR-34a acts as tumor suppressor microRNA (miRNA) in several cancers, including multiple myeloma (MM), by controlling the expression of target proteins involved in cell cycle, differentiation and apoptosis. Here, we have investigated the combination between miR-34a and γ-secretase inhibitor (γSI), Sirtinol or zoledronic acid (ZOL) in order to enhance the inhibitory action of this miRNA on its canonical targets such as Notch1 and SIRT1, and on Ras/MAPK-dependent pathways. Our data demonstrate that miR-34a synthetic mimics significantly enhance the anti-tumor activity of all the above-mentioned anti-cancer agents in RPMI 8226 MM cells. We found that γSI enhanced miR-34a-dependent anti-tumor effects by activating the extrinsic apoptotic pathway which could overcome the cytoprotective autophagic mechanism. Moreover, the combination between miR-34a and γSI increased the cell surface calreticulin (CRT) expression, that is well known for triggering anti-tumor immunological response. The combination between miR-34a and Sirtinol induced the activation of an intrinsic apoptotic pathway along with increased surface expression of CRT. Regarding ZOL, we found a powerful growth inhibition after enforced miR-34a expression, which was not likely attributable to neither apoptosis nor autophagy modulation. Based on our data, the combination of miR-34a with other anti-cancer agents appears a promising anti-MM strategy deserving further investigation.

Citace poskytuje Crossref.org

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$a Misso, Gabriella $u Department of Biochemistry, Biophysics and General Pathology, University of Campania "L. Vanvitelli", Naples, Italy.
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$a Grimaldi, Anna $u Department of Biochemistry, Biophysics and General Pathology, University of Campania "L. Vanvitelli", Naples, Italy.
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$a Zappavigna, Silvia $u Department of Biochemistry, Biophysics and General Pathology, University of Campania "L. Vanvitelli", Naples, Italy.
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$a Russo, Margherita $u Department of Biochemistry, Biophysics and General Pathology, University of Campania "L. Vanvitelli", Naples, Italy.
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$a Amler, Evzen $u Institute of Biophysics, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. Laboratory of Tissue Engineering, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.
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$a Di Martino, Maria Teresa $u Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, Catanzaro, Italy.
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$a Caraglia, Michele $u Department of Biochemistry, Biophysics and General Pathology, University of Campania "L. Vanvitelli", Naples, Italy. Michele.caraglia@unicampania.it. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA. Michele.caraglia@unicampania.it.
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