DHX9/DNA-tandem repeat-dependent downregulation of ciRNA-Fmn1 in the dorsal horn is required for neuropathic pain  

作　　者：Xiao-dan Liu Tong Jin Yang Tao Ming Zhang Hong-li Zheng Qiao-qiao Liu Ke-hui Yang Ru-na Wei Si-yuan Li Yue Huang Zhou-ya Xue Ling-yun Hao Qi-hui Wang Li Yang Fu-qing Lin Wen Shen Yuan-xiang Tao Hong-jun Wang Jun-li Cao Zhi-qiang Pan 

机构地区：[1]Jiangsu Province Key Laboratory of Anesthesiology,Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology,NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs,Xuzhou Medical University,Xuzhou,221004,China [2]Department of Anesthesiology,The Sixth Affiliated Hospital of Guangzhou Medical University,Qingyuan People’s Hospital,Qingyuan,511518,China [3]Department of Pain,Shanghai Tenth People’s Hospital,Tongji University,Shanghai,200072,China [4]Department of Anesthesiology,Yancheng Affiliated Hospital of Xuzhou Medical University,Yancheng,224001,China [5]Department of Pain,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,221006,China [6]Department of Anesthesiology,New Jersey Medical School,Rutgers,The State University of New Jersey,Newark,NJ,USA

出　　处：《Acta Pharmacologica Sinica》2023年第9期1748-1767,共20页中国药理学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (82171234,81971041,81671096 to ZQP,82171233 to HJW,82201391 to QHW,32200818 to LY,81901132 to ZYX);Jiang Su-Specially Appointed Professor Project,Natural Science Foundation of Jiangsu Province (BK20201460);Key project of the Natural Science Foundation of Jiangsu Education Department (22KJA320008);Key Project of Shanghai Chongming District (CKY2019-1).

摘　　要：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.

关 键 词：ciRNA-Fmn 1 DHX9 ALBUMIN UBR5 neuropathic pain 

分 类 号：R96[医药卫生—药理学]