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LncRNA XR_351665 contributes to chronic pain-induced depression by upregulating DNMT1 via sponging miR-152-3p

  • Author Footnotes
    # Xiaobao Ding, Yuwen Lin and Binbin Yan contributed equally.
    Xiaobao Ding
    Footnotes
    # Xiaobao Ding, Yuwen Lin and Binbin Yan contributed equally.
    Affiliations
    Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China
    Search for articles by this author
  • Author Footnotes
    # Xiaobao Ding, Yuwen Lin and Binbin Yan contributed equally.
    Yuwen Lin
    Footnotes
    # Xiaobao Ding, Yuwen Lin and Binbin Yan contributed equally.
    Affiliations
    Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China
    Search for articles by this author
  • Author Footnotes
    # Xiaobao Ding, Yuwen Lin and Binbin Yan contributed equally.
    Binbin Yan
    Footnotes
    # Xiaobao Ding, Yuwen Lin and Binbin Yan contributed equally.
    Affiliations
    Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China
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  • Xiaowei Jiao
    Affiliations
    Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China
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  • Qiang Liu
    Affiliations
    Jiangsu Province Key Laboratory of Anesthesiology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, 221004, China
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  • Huihui Miao
    Affiliations
    Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
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  • Yuqing Wu
    Affiliations
    Jiangsu Province Key Laboratory of Anesthesiology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, 221004, China
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  • Chenghua Zhou
    Correspondence
    Corresponding author: Chenghua Zhou
    Affiliations
    Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China
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  • Author Footnotes
    # Xiaobao Ding, Yuwen Lin and Binbin Yan contributed equally.
Published:October 14, 2022DOI:https://doi.org/10.1016/j.jpain.2022.10.006

      Highlights

      • LncRNA XR_351665 in the central amygdala is involved in chronic pain-induced depression.
      • MiR-152-3p/DNMT1 is the downstream target of lncRNA-XR _351665.
      • LncRNA XR_351665 upregulates DNMT1 via sponging miR-152-3p in chronic pain-induced depression.

      Abstract

      Chronic pain is frequently comorbid with depression. However, the mechanisms underlying chronic pain-induced depression remain unclear. Here, we found that DNA methyltransferase 1 (DNMT1) was upregulated in the central amygdala (CeA) of spared nerve injury (SNI)-induced chronic pain-depression rats, and knockdown of DNMT1 could improve the depression-like behaviors in SNI rats. Additionally, a panel of differentially expressed lncRNAs, including 38 upregulated and 12 downregulated lncRNAs, were identified by microarray analysis. Bioinformatics analysis suggested that the upregulated lncRNA XR_351665 was the upstream molecule to regulate DNMT1 expression. The knockdown of XR_351665 significantly alleviated the depression-like behaviors in SNI rats, whereas overexpression of XR_351665 induced the depression-like behaviors in naïve rats. Further mechanism-related researches uncovered that XR_351665 functioned as a competing endogenous RNA (ceRNA) to upregulate DNMT1 by competitively sponging miR-152-3p, and subsequently promoted the development of chronic pain-induced depression. Our findings suggest that lncRNA XR_351665 is involved in the development of chronic pain-induced depression by upregulating DNMT1 via sponging miR-152-3p. These data provide novel insight into understanding the pathogenesis of chronic pain-induced depression and identify a potential therapeutic target.

      Keywords

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