Huang Chung-Ming, Chen Yu-Chia, Lai I-Lu, Chen Hong-Da, Huang Po-Hao, Tu Siang-Jyun, Lee Ya-Ting, Yen Ju-Chen, Lin Chia-Li, Liu Ting-Yuan, Chang Jan-Gowth
Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan.
Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Front Med (Lausanne). 2022 Sep 6;9:889464. doi: 10.3389/fmed.2022.889464. eCollection 2022.
Hyperuricemia and gout are two of the most common metabolic disorders worldwide; their incidence is increasing with changes in lifestyle, and they are correlated with many diseases, including renal and cardiovascular diseases. The majority of studies on hyperuricemia and gout have focused on the discovery of the associated genes and their functions and on the roles of monocytes and neutrophils in the development of gout. Virtually no studies investigating the epigenomics of gout disease or exploring the clinical significance of such research have been conducted. In this study, we observed that the expression of enzymes involved in RNA modifications or RNA editing was affected in uric acid (UA)- or monosodium urate (MSU)-treated cell lines. RNA alternative splicing and splicing factors were also affected by UA or MSU treatment. We used transcriptome sequencing to analyze genome-wide RNA splicing and RNA editing and found significant changes in RNA splicing and RNA editing in MSU- or UA-treated THP-1 and HEK293 cells. We further found significant changes of RNA modifications, editing, and splicing in patients with gout. The data indicate that RNA modifications, editing, and splicing play roles in gout. The findings of this study may help to understand the mechanism of RNA splicing and modifications in gout, facilitating the development of new diagnostic and therapeutic strategies.
高尿酸血症和痛风是全球最常见的两种代谢性疾病;随着生活方式的改变,其发病率不断上升,并且它们与包括肾脏和心血管疾病在内的许多疾病相关。大多数关于高尿酸血症和痛风的研究都集中在相关基因及其功能的发现以及单核细胞和中性粒细胞在痛风发展中的作用上。实际上,尚未开展关于痛风疾病表观基因组学或探索此类研究临床意义的研究。在本研究中,我们观察到在尿酸(UA)或尿酸钠(MSU)处理的细胞系中,参与RNA修饰或RNA编辑的酶的表达受到影响。RNA可变剪接和剪接因子也受到UA或MSU处理的影响。我们使用转录组测序来分析全基因组的RNA剪接和RNA编辑,发现在MSU或UA处理的THP-1和HEK293细胞中RNA剪接和RNA编辑有显著变化。我们进一步发现痛风患者的RNA修饰、编辑和剪接有显著变化。数据表明RNA修饰、编辑和剪接在痛风中起作用。本研究结果可能有助于理解痛风中RNA剪接和修饰的机制,促进新诊断和治疗策略的开发。