Genome-wide identification and functional analyses of microRNA signatures associated with cancer pain
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...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
18 October 2013
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| In: |
EMBO molecular medicine
Year: 2013, Jahrgang: 5, Heft: 11, Pages: 1740-1758 |
| ISSN: | 1757-4684 |
| DOI: | 10.1002/emmm.201302797 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/emmm.201302797 Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.1002/emmm.201302797 
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| Verfasserangaben: | Kiran Kumar Bali, Deepitha Selvaraj, Venkata P. Satagopam, Jianning Lu, Reinhard Schneider, Rohini Kuner |
| Zusammenfassung: | 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. |
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| Beschreibung: | Gesehen am 13.11.2020 |
| Beschreibung: | Online Resource |
| ISSN: | 1757-4684 |
| DOI: | 10.1002/emmm.201302797 |