Background As a type of chronic autoimmune joint disease, rheumatoid arthritis (RA) is a disorder, characterized by a variety of physical symptoms as well as RA fibroblast-like synoviocyte (RA-FLS) proliferation. More recently, long non-coding RNAs (lncRNAs) have been implicated in the progression of various diseases including the progression of RA. Hence, the aim of the current study was to investigate the role by which the lncRNA, plasmacytoma variant translocation 1 (PVT1), influences RA-FLSs and its ability to modulate the methylation of sirtuin 6 (sirt6). Methods RA rat models were initially established to determine the expression of PVT1 and sirt6 in synovial tissues and RA-FLSs. Elevation or depletion of PVT1 or sirt6 was achieved by means of transformation with plasmids in order to investigate their effects on RA-FLS proliferation, inflammation and apoptosis. The localization of PVT1 and its binding ability to the sirt6 promoter region were also explored in an attempt to elucidate the correlation between PVT1 and sirt6 methylation. Results High expression of PVT1 and low expression of sirt6 were detected in the synovial tissues and RA-FLSs of the rat models. RA-FLSs treated with sh-PVT1 or oe-sirt6 exhibited suppressed cell proliferation, inflammation and induced apoptosis. PVT1 was predominately localized in the nucleus while evidence was obtained indicating that it could bind to the sirt6 promoter to induce sirt6 methylation, thus inhibiting sirt6 transcription. PVT1 knockdown was observed to restore sirt6 expression through decreasing sirt6 methylation, thereby alleviating RA. Conclusion The key findings of the study provide evidence suggesting that, PVT1 knockdown is able to restrain RA progression by inhibiting sirt6 methylation to restore its expression.

中文翻译：

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长链非编码 RNA PVT1 敲低通过 sirt6 的去甲基化抑制成纤维细胞样滑膜细胞炎症并诱导类风湿关节炎细胞凋亡。

背景作为一种慢性自身免疫性关节病，类风湿关节炎（RA）是一种以多种躯体症状和RA成纤维细胞样滑膜细胞（RA-FLS）增殖为特征的疾病。最近，长链非编码 RNA (lncRNA) 与各种疾病的进展有关，包括 RA 的进展。因此，本研究的目的是研究 lncRNA、浆细胞瘤变体易位 1 (PVT1) 影响 RA-FLS 的作用及其调节 sirtuin 6 (sirt6) 甲基化的能力。方法 初步建立RA大鼠模型，测定滑膜组织和RA-FLSs中PVT1和sirt6的表达。PVT1 或 sirt6 的升高或消耗是通过用质粒转化来实现的，以研究它们对 RA-FLS 增殖的影响，炎症和细胞凋亡。还探索了 PVT1 的定位及其与 sirt6 启动子区域的结合能力，以试图阐明 PVT1 和 sirt6 甲基化之间的相关性。结果大鼠模型的滑膜组织和RA-FLSs中均检测到PVT1高表达，sirt6低表达。用 sh-PVT1 或 oe-sirt6 处理的 RA-FLS 表现出抑制的细胞增殖、炎症和诱导的细胞凋亡。PVT1 主要定位在细胞核中，而获得的证据表明它可以与 sirt6 启动子结合以诱导 sirt6 甲基化，从而抑制 sirt6 转录。观察到 PVT1 敲低通过降低 sirt6 甲基化来恢复 sirt6 表达，从而减轻 RA。结论 该研究的主要发现提供的证据表明，