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miR-34a-mediated regulation of XIST in female cells under inflammation
Journal article   Open access   Peer reviewed

miR-34a-mediated regulation of XIST in female cells under inflammation

Botros B. Shenoda, Yuzhen Tian, Guillermo M. Alexander, Enrique Aradillas-Lopez, Robert J. Schwartzman and Seena K. Ajit
Journal of pain research, v 11, pp 935-945
01 Jan 2018
PMID: 29773953
url
https://doi.org/10.2147/jpr.s159458View
Published, Version of Record (VoR)CC BY-NC V4.0 Open
url
https://doi.org/10.2147/JPR.S159458View
Published, Version of Record (VoR) Open

Abstract

Clinical Neurology Life Sciences & Biomedicine Neurosciences & Neurology Science & Technology
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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Clinical Neurology
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