关键词: Cancer-induced bone pain Epitranscriptomic profiling Spinal dorsal horn ac4C acetylation

Mesh : Rats Animals Acetylation RNA / metabolism Cancer Pain / genetics complications Bone Neoplasms / complications genetics metabolism Spinal Cord Dorsal Horn / metabolism

来  源:   DOI:10.1177/17448069231178487   PDF(Pubmed)

Abstract:
Recently, epigenetics involved in the regulation of gene expression has become a research hotspot. This study evaluated N4-acetylcytidine (ac4c) RNA acetylation in the spinal dorsal horn (SDH) of rats with cancer-induced bone pain (CIBP). The ac4C-specific RIP sequencing and NAT10-specific RIP sequencing were performed to identify the differences in ac4C acetylation and gene expression in the SDH between CIBP and sham groups, the relationship with the acetylation-modifying enzyme NAT10, and association analysis was performed. By interfering with the NAT10 expression, the relationship between some up-regulated genes and ac4C acetylation in CIBP was verified. In this study, we demonstrated that bone cancer increases the levels of NAT10 and the overall acetylation, inducing differential ac4C patterns in the SDH of rats. Through verification experiments, it was found that ac4C acetylation of some genes is regulated by NAT10, and differential ac4C patterns in RNA determine the expression of this RNA. We exposed that some CIBP-related gene expression was altered in the SDH of rats, which was regulated by differentially expressed ac4C acetylation.
摘要:
最近,表观遗传学参与基因表达调控已成为研究热点。这项研究评估了患有癌症诱发的骨痛(CIBP)的大鼠脊髓背角(SDH)中的N4-乙酰胞苷(ac4c)RNA乙酰化。进行了ac4C特异性RIP测序和NAT10特异性RIP测序,以确定CIBP和假手术组之间在SDH中ac4C乙酰化和基因表达的差异,与乙酰化修饰酶NAT10的关系,并进行关联分析。通过干扰NAT10表达,部分上调基因与CIBP中ac4C乙酰化的关系得到验证。在这项研究中,我们证明骨癌会增加NAT10水平和整体乙酰化,在大鼠SDH中诱导差异ac4C模式。通过验证实验,发现某些基因的ac4C乙酰化受NAT10调节,RNA中的差异ac4C模式决定了该RNA的表达。我们发现someCI的BP相关基因表达在大鼠的SDH中发生了改变,受差异表达的ac4C乙酰化调节。
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