Genome-wide identification and functional analyses of microRNA signatures associated with cancer pain

• Verfasst von: Bali, Kiran Kumar [VerfasserIn]
• Verfasst von: Selvaraj, Deepitha [VerfasserIn]
• Verfasst von: Satagopam, Venkata* [VerfasserIn]
• Verfasst von: Lu, Jianning [VerfasserIn]
• Verfasst von: Schneider, Reinhard [VerfasserIn]
• Verfasst von: Kuner, Rohini [VerfasserIn]
• Titel: Genome-wide identification and functional analyses of microRNA signatures associated with cancer pain
• Verf.angabe: Kiran Kumar Bali, Deepitha Selvaraj, Venkata P. Satagopam, Jianning Lu, Reinhard Schneider, Rohini Kuner
• E-Jahr: 2013
• Jahr: 18 October 2013
• Umfang: 19 S.
• Fussnoten: Gesehen am 13.11.2020
• Titel Quelle: Enthalten in: European Molecular Biology OrganizationEMBO molecular medicine
• Ort Quelle: Weinheim : Wiley-VCH, 2009
• Jahr Quelle: 2013
• Band/Heft Quelle: 5(2013), 11, Seite 1740-1758
• ISSN Quelle: 1757-4684
• DOI: doi:10.1002/emmm.201302797
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: bone metastatic pain
• Sach-SW: Clcn3
• Sach-SW: gene regulation
• Sach-SW: miRNA inhibitors
• Sach-SW: miRNA mimics
• K10plus-PPN: 1738657787

Abstract

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.