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首页> 外文期刊>RSC Advances >Gm5820, an antisense RNA of FGF1, suppresses FGF1 expression at the posttranscriptional level to inactivate the ERK/STAT3 pathway and alleviates neuropathic pain in mice
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Gm5820, an antisense RNA of FGF1, suppresses FGF1 expression at the posttranscriptional level to inactivate the ERK/STAT3 pathway and alleviates neuropathic pain in mice

机译：Gm5820是FGF1的反义RNA，可在转录后水平上抑制FGF1的表达，从而使ERK / STAT3途径失活并减轻小鼠的神经性疼痛

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Emerging evidence reveals that lncRNAs play important roles in various pathological processes, but precious little indicates their regulatory role in neuropathic pain. In this study, we performed unbiased whole transcriptome profiling in dorsal root ganglions (DRGs) from mice with sham operation and mice with chronic constriction injury (CCI). Gm5820 was one of the most downregulated RNA transcripts in CCI neuropathic pain model mice. Then, a pcDNA-Gm5820 expression vector was constructed and administered into CCI mice through intrathecal injection. The results showed that upregulation of Gm5820 alleviated mouse mechanical allodynia and thermal/cold hyperalgesia, and reduced the accumulation of inflammatory cytokines and ROS in the DRG tissue. Moreover, different concentrations of pcDNA-Gm5820 expression vector and Gm5820 siRNA were respectively transfected into primary DRG neurons from 4 ~(th) to 6 ~(th) lumbar vertebra (L4–L6). We found that Gm5820 overexpression improved cell viability and migration, and reduced the production of ROS, LDH and IL-1β. In contrast, Gm5820 knockdown had the opposite effects. Furthermore, RNA pull-down assays with FGF1 and Gm5820 cDNA probes both demonstrated that FGF1 mRNA and Gm5820 directly bound to each other. Moreover, Gm5820 negatively regulated the stability of FGF1 mRNA. Gm5820 suppressed the expression of FGF1 at the post-transcriptional level and negatively regulated the activation of ERK1/2-mediated STAT3, a critical contributor in neuropathic pain. In conclusion, Gm5820 directly binds to FGF1 mRNA and suppresses FGF1 expression at the posttranscriptional level, it functions as a negative regulator in the activation of the ERK/STAT3 pathway, and upregulation of Gm5820 alleviates neuropathic pain in CCI mice.
机译：新兴证据表明，lncRNA在各种病理过程中均起重要作用，但很少有迹象表明其在神经性疼痛中的调节作用。在这项研究中，我们对假手术小鼠和慢性收缩损伤小鼠（CCI）的背根神经节（DRG）进行了无偏见的完整转录组分析。 Gm5820是CCI神经性疼痛模型小鼠中表达最下调的RNA之一。然后，构建pcDNA-Gm5820表达载体，并通过鞘内注射将其给予CCI小鼠。结果表明，Gm5820的上调减轻了小鼠的机械性异常性疼痛和热/冷痛觉过敏，并减少了DRG组织中炎性细胞因子和ROS的积累。此外，将不同浓度的pcDNA-Gm5820表达载体和Gm5820 siRNA分别从第4个到第6个腰椎（L4-L6）转染到原代DRG神经元中。我们发现，Gm5820过表达改善了细胞活力和迁移，并减少了ROS，LDH和IL-1β的产生。相反，Gm5820的组合产生相反的效果。此外，使用FGF1和Gm5820 cDNA探针进行RNA下拉分析均表明FGF1 mRNA和Gm5820直接相互结合。此外，Gm5820负调节FGF1 mRNA的稳定性。 Gm5820在转录后水平抑制FGF1的表达，并负调节ERK1 / 2介导的STAT3的激活，而STAT3是神经性疼痛的关键因素。总之，Gm5820直接与FGF1 mRNA结合并在转录后水平上抑制FGF1表达，在ERK / STAT3途径的激活中起负调节剂的作用，而Gm5820的上调可减轻CCI小鼠的神经性疼痛。

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