@article{APS10883,
author = {Xiao-dan Liu and Tong Jin and Yang Tao and Ming Zhang and Hong-li Zheng and Qiao-qiao Liu and Ke-hui Yang and Ru-na Wei and Si-yuan Li and Yue Huang and Zhou-ya Xue and Ling-yun Hao and Qi-hui Wang and Li Yang and Fu-qing Lin and Wen Shen and Yuan-xiang Tao and Hong-jun Wang and Jun-li Cao and Zhi-qiang Pan},
title = {DHX9/DNA-tandem repeat-dependent downregulation of ciRNA-Fmn1 in the dorsal horn is required for neuropathic pain},
journal = {Acta Pharmacologica Sinica},
volume = {44},
number = {9},
year = {2023},
keywords = {},
abstract = {Circular RNAs (ciRNAs) are emerging as new players in the regulation of gene expression. However, how ciRNAs are involved in neuropathic pain is poorly understood. Here, we identify the nervous-tissue-specific ciRNA-Fmn1 and report that changes in ciRNA-Fmn1 expression in spinal cord dorsal horn neurons play a key role in neuropathic pain after nerve injury. ciRNA-Fmn1 was significantly downregulated in ipsilateral dorsal horn neurons after peripheral nerve injury, at least in part because of a decrease in DNA helicase 9 (DHX9), which regulates production of ciRNA-Fmn1 by binding to DNA-tandem repeats. Blocking ciRNA-Fmn1 downregulation reversed nerve-injury-induced reductions in both the binding of ciRNA-Fmn1 to the ubiquitin ligase UBR5 and the level of ubiquitination of albumin (ALB), thereby abrogating the nerve-injury-induced increase of ALB expression in the dorsal horn and attenuating the associated pain hypersensitivities. Conversely, mimicking downregulation of ciRNA-Fmn1 in naïve mice reduced the UBR5-controlled ubiquitination of ALB, leading to increased expression of ALB in the dorsal horn and induction of neuropathic-pain-like behaviors in naïve mice. Thus, ciRNA-Fmn1 downregulation caused by changes in binding of DHX9 to DNA-tandem repeats contributes to the genesis of neuropathic pain by negatively modulating UBR5-controlled ALB expression in the dorsal horn.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10883}
}