Article (Scientific journals)
Genome-wide identification and functional analyses of microRNA signatures associated with cancer pain.
Bali, Kiran Kumar; Selvaraj, Deepitha; Satagopam, Venkata et al.
2013In EMBO Molecular Medicine, 5 (11), p. 1740-58
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Keywords :
Clcn3; bone metastatic pain; gene regulation; miRNA inhibitors; miRNA mimics
Abstract :
[en] Cancer pain remains a major challenge and there is an urgent demand for the development of specific mechanism-based therapies. Various diseases are associated with unique signatures of expression of microRNAs (miRNAs), which reveal deep insights into disease pathology. Using a comprehensive approach combining genome-wide miRNA screening, molecular and in silico analyses with behavioural approaches in a clinically relevant model of metastatic bone-cancer pain in mice, we now show that tumour-induced conditions are associated with a marked dysregulation of 57 miRNAs in sensory neurons corresponding to tumour-affected areas. By establishing protocols for interference with disease-induced miRNA dysregulation in peripheral sensory neurons in vivo, we functionally validate six dysregulated miRNAs as significant modulators of tumour-associated hypersensitivity. In silico analyses revealed that their predicted targets include key pain-related genes and we identified Clcn3, a gene encoding a chloride channel, as a key miRNA target in sensory neurons, which is functionally important in tumour-induced nociceptive hypersensitivity in vivo. Our results provide new insights into endogenous gene regulatory mechanisms in cancer pain and open up attractive and viable therapeutic options.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bali, Kiran Kumar
Selvaraj, Deepitha
Satagopam, Venkata ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Lu, Jianning
Schneider, Reinhard ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Kuner, Rohini
Language :
English
Title :
Genome-wide identification and functional analyses of microRNA signatures associated with cancer pain.
Publication date :
2013
Journal title :
EMBO Molecular Medicine
ISSN :
1757-4684
Publisher :
Wiley-Blackwell, United Kingdom
Volume :
5
Issue :
11
Pages :
1740-58
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.
Available on ORBilu :
since 26 July 2014

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