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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00487374" target="_blank" >RIV/68378041:_____/17:00487374 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/17:10373395

Result on the web

<a href="http://dx.doi.org/10.1038/s41598-017-18186-0" target="_blank" >http://dx.doi.org/10.1038/s41598-017-18186-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-017-18186-0" target="_blank" >10.1038/s41598-017-18186-0</a>

Result language

angličtina

Original language name

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

Original language description

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 gamma-secretase inhibitor (gamma SI), 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 gamma SI 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 gamma SI 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30403 - Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions [pharmacogenomics, gene-based therapeutics])

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

dec

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

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UT code for WoS article

000418389000009

EID of the result in the Scopus database

2-s2.0-85038872378