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Title

Functional high‑throughput screening reveals miR‑323a‑5p and miR‑342‑5p as new tumor‑suppressive microRNA for neuroblastoma

AuthorsSoriano, Aroa; Masanas, Marc; Boloix, Ariadna; Masiá, Núria; París Coderch, Laia; Piskareva, Olga; Jiménez, Carlos; Henrich, Kai‑Oliver; Roma, Josep; Westermann, Frank; Stallings, Raymond L.; Sábado, Constantino; Sánchez de Toledo, Josep; Santamaria, Anna; Gallego, Soledad; Segura, Miguel F.
Issue Date15-Feb-2019
AbstractCurrent therapies for most non-infectious diseases are directed at or affect functionality of the human translated genome, barely 2% of all genetic information. By contrast, the therapeutic potential of targeting the transcriptome, ~ 70% of the genome, remains largely unexplored. RNA therapeutics is an emerging field that widens the range of druggable targets and includes elements such as microRNA. Here, we sought to screen for microRNA with tumor-suppressive functions in neuroblastoma, an aggressive pediatric tumor of the sympathetic nervous system that requires the development of new therapies. We found miR-323a-5p and miR-342-5p to be capable of reducing cell proliferation in multiple neuroblastoma cell lines in vitro and in vivo, thereby providing a proof of concept for miRNA-based therapies for neuroblastoma. Furthermore, the combined inhibition of the direct identified targets such as CCND1, CHAF1A, INCENP and BCL-XL could reveal new vulnerabilities of high-risk neuroblastoma.
Publisher version (URL)http://dx.doi.org/10.1007/s00018-019-03041-4
URIhttp://hdl.handle.net/10261/203384
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