Format

Send to

Choose Destination
Cell Mol Life Sci. 2019 Feb 15. doi: 10.1007/s00018-019-03041-4. [Epub ahead of print]

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

Author information

1
Group of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute (VHIR)-Universitat Autònoma de Barcelona (UAB), Passeig Vall d'Hebron 119-129, Collserola Building. Lab 207, 08035, Barcelona, Spain.
2
Institut de Ciència de Materials de Barcelona (ICMAB-CSIC) and Nanomol Technologies SA, Mòdul de Recerca B, Campus UAB, 08193, Bellaterra, Spain.
3
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR)-Universitat Autònoma de Barcelona (UAB), Passeig Vall d'Hebron 119, 08035, Barcelona, Spain.
4
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland and National Children's Research Centre Our Lady's Children's Hospital, Dublin, Ireland.
5
Neuroblastoma Genomics Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
6
Pediatric Oncology and Hematology Department, Hospital Universitari Vall d'Hebron-Universitat Autònoma de Barcelona (UAB), Passeig Vall d'Hebron 119, 08035, Barcelona, Spain.
7
Group of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute (VHIR)-Universitat Autònoma de Barcelona (UAB), Passeig Vall d'Hebron 119-129, Collserola Building. Lab 207, 08035, Barcelona, Spain. miguel.segura@vhir.org.

Abstract

Current 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.

KEYWORDS:

14q32; Cancer therapy; Epigenetics; High-throughput screening; Non-coding RNA; Pediatric cancer

PMID:
30770954
DOI:
10.1007/s00018-019-03041-4

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center