MicroRNA cluster miR-17-92 regulates multiple functionally related voltage-gated potassium channels in chronic neuropathic pain View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-07-05

AUTHORS

Atsushi Sakai, Fumihito Saitow, Motoyo Maruyama, Noriko Miyake, Koichi Miyake, Takashi Shimada, Takashi Okada, Hidenori Suzuki

ABSTRACT

miR-17-92 is a microRNA cluster with six distinct members. Here, we show that the miR-17-92 cluster and its individual members modulate chronic neuropathic pain. All cluster members are persistently upregulated in primary sensory neurons after nerve injury. Overexpression of miR-18a, miR-19a, miR-19b and miR-92a cluster members elicits mechanical allodynia in rats, while their blockade alleviates mechanical allodynia in a rat model of neuropathic pain. Plausible targets for the miR-17-92 cluster include genes encoding numerous voltage-gated potassium channels and their modulatory subunits. Single-cell analysis reveals extensive co-expression of miR-17-92 cluster and its predicted targets in primary sensory neurons. miR-17-92 downregulates the expression of potassium channels, and reduced outward potassium currents, in particular A-type currents. Combined application of potassium channel modulators synergistically alleviates mechanical allodynia induced by nerve injury or miR-17-92 overexpression. miR-17-92 cluster appears to cooperatively regulate the function of multiple voltage-gated potassium channel subunits, perpetuating mechanical allodynia. More... »

PAGES

16079

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms16079

DOI

http://dx.doi.org/10.1038/ncomms16079

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090345019

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28677679


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