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miR-15b mediates oxaliplatin-induced chronic neuropathic pain through BACE1 down-regulation.

Authors: Ito, Naomi  Sakai, Atsushi  Miyake, Noriko  Maruyama, Motoyo  Iwasaki, Hirotoshi  Miyake, Koichi  Okada, Takashi  Sakamoto, Atsuhiro  Suzuki, Hidenori 
Citation: Ito N, etal., Br J Pharmacol. 2017 Mar;174(5):386-395. doi: 10.1111/bph.13698. Epub 2017 Jan 23.
Pubmed: (View Article at PubMed) PMID:28012171
DOI: Full-text: DOI:10.1111/bph.13698

BACKGROUND AND PURPOSE: Although oxaliplatin is an effective anti-cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although miRNAs have been increasingly recognized as important modulators in a variety of pain conditions, their involvement in chemotherapy-induced neuropathic pain is unknown.
EXPERIMENTAL APPROACH: Oxaliplatin-induced chronic neuropathic pain was induced in rats by i.p. injections of oxaliplatin (2 mg·kg-1 ) for five consecutive days. The expression levels of miR-15b and ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1 also known as ß-secretase 1) were examined in the dorsal root ganglion (DRG). To examine the function of miR-15b, an adeno-associated viral vector encoding miR-15b was injected into the DRG in vivo.
KEY RESULTS: Among the miRNAs examined in the DRG in the late phase of oxaliplatin-induced neuropathic pain, miR-15b was most robustly increased. Our in vitro assay results determined that BACE1 was a target of miR-15b. BACE1 and miR-15b were co-expressed in putative myelinated and unmyelinated DRG neurons. Overexpression of miR-15b in DRG neurons caused mechanical allodynia in association with reduced expression of BACE1. Consistent with these results, a BACE1 inhibitor dose-dependently induced significant mechanical allodynia.
CONCLUSIONS AND IMPLICATIONS: These findings suggest that miR-15b contributes to oxaliplatin-induced chronic neuropathic pain at least in part through the down-regulation of BACE1.


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RGD Object Information
RGD ID: 13782150
Created: 2018-08-23
Species: All species
Last Modified: 2018-08-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.