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Journal article
miR-34a-mediated regulation of XIST in female cells under inflammation
Journal of pain research, Vol.11, pp.935-945
01 Jan 2018
PMCID: PMC5947841
PMID: 29773953
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Evidence is overwhelming for sex differences in pain, with women representing the majority of the chronic pain patient population. There is a need to explore novel avenues to elucidate this sex bias in the development of chronic inflammatory pain conditions. Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder, and the incidence of CRPS is greater in women than in men by similar to 4:1. Since neurogenic inflammation is a key feature of CRPS, dysregulation of inflammatory responses can be a factor in predisposing women to chronic pain.
Methods: Our studies investigating alterations in circulating microRNAs (miRNAs) in whole blood from female CRPS patients showed significant differential expression of miRNAs between responders and poor responders to ketamine treatment. Several of these miRNAs are predicted to target the long noncoding RNA, X-inactive-specific transcript (XIST). XIST mediates X-chromosome inactivation and is essential for equalizing the expression of X-linked genes between females and males. Based on the well-established role in inflammatory process, we focused on miR-34a, one of the miRNAs predicted to target XIST, and downregulated in CRPS patients responding poorly to ketamine.
Results: Our in vitro and in vivo models of acute inflammation and data from patients with CRPS showed that miR-34a can regulate XIST under inflammation directly, and through pro-inflammatory transcription factor Yin-Yang 1 (YY1). XIST was significantly upregulated in a subset of CRPS patients responding poorly to ketamine.
Conclusion: Since dysregulation of XIST can result in genes escaping inactivation or reactivation in female cells, further investigations on the role of XIST in the predominance of chronic inflammatory and pain disorders in women is warranted.
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Details
- Title
- miR-34a-mediated regulation of XIST in female cells under inflammation
- Creators
- Botros B. Shenoda - Drexel UniversityYuzhen Tian - Drexel UniversityGuillermo M. Alexander - Drexel UniversityEnrique Aradillas-Lopez - Drexel UniversityRobert J. Schwartzman - Drexel UniversitySeena K. Ajit - Drexel University
- Publication Details
- Journal of pain research, Vol.11, pp.935-945
- Publisher
- Dove Medical Press Ltd
- Number of pages
- 11
- Grant note
- R01NS102836 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Drexel University Clinical and Translational Research Institute Fulbright Foreign Student Program fellowship - US Department of State, Bureau of Educational and Cultural Affairs 1R01NS102836-01A1 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Drexel University College of Medicine Rita Allen Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]; Neurology; Pharmacology and Physiology
- Identifiers
- 991019167583404721
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- Clinical Neurology