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Abstract：
The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) level was demonstrated as involved in pediatric inflammatory bowel disease (IBD) pathogenesis. Since its antisense transcript GAS5-AS1 has never been investigated in IBD, this study aims to detect whether GAS5-AS1 and GAS5 levels are related to IBD clinical parameters and investigate their correlation in vitro. Twenty-six IBD pediatric patients were enrolled; paired inflamed and non-inflamed intestinal biopsies were collected. We evaluated GAS5 and GAS5-AS1 levels by real-time PCR. The role of GAS5 and GAS5-AS1 was assessed in vitro by transient silencing in THP1-derived macrophages. GAS5-AS1 and GAS5 levels were associated with patients\' clinical parameters; GAS5-AS1 expression was downregulated in inflamed tissues and inversely correlated with disease activity. A positive correlation between GAS5-AS1 and GAS5 levels was observed in non-inflamed biopsies. On THP1-derived macrophages, a reduced amount of both GAS5-AS1 and GAS5 was observed; accordingly, matrix metalloproteinase (MMP) 9 was increased. After GAS5-AS1 silencing, a downregulation of GAS5 was found, whereas no effect was detected on GAS5-AS1 after GAS5 silencing. Conclusion: This study provided for the first time new insights into the potential role of GAS5-AS1 in IBD. GAS5-AS1 modulates GAS5 levels in vitro and may serve as a potential IBD diagnostic biomarker. What is Known: • GAS5 is involved in regulating intestinal MMP-2 and MMP-9 in pediatric patients with IBD; • GAS5-AS1 has never been investigated in the context of IBD; • GAS5-AS1 regulates the expression of GAS5, increasing its stability in tissues and in vitro cell models of cancer. What is New: • GAS5-AS1 correlated with GAS5 and IBD clinical parameters; • GAS5-AS1 can modulate GAS5 levels in macrophages; • GAS5-AS1 may serve as potential IBD diagnostic biomarker.
摘要：
长非编码RNA（lncRNA）生长停滞特异性转录物5（GAS5）水平被证明与小儿炎症性肠病（IBD）发病机理有关。由于其反义转录物GAS5-AS1从未在IBD中进行过研究，这项研究旨在检测GAS5-AS1和GAS5水平是否与IBD临床参数相关，并探讨其在体外的相关性。纳入26例IBD儿科患者；收集成对的发炎和非发炎肠活检。我们通过实时PCR评估了GAS5和GAS5-AS1水平。通过在THP1衍生的巨噬细胞中的瞬时沉默在体外评估GAS5和GAS5-AS1的作用。GAS5-AS1和GAS5水平与患者临床参数相关；GAS5-AS1表达在发炎组织中下调，与疾病活动负相关。在非炎症活检中观察到GAS5-AS1和GAS5水平之间的正相关。在THP1来源的巨噬细胞上，观察到GAS5-AS1和GAS5的量减少；因此，基质金属蛋白酶(MMP)9升高。GAS5-AS1沉默后，发现了GAS5的下调，而GAS5沉默后对GAS5-AS1无影响。结论：本研究首次为GAS5-AS1在IBD中的潜在作用提供了新的见解。GAS5-AS1在体外调节GAS5水平并且可以用作潜在的IBD诊断生物标志物。已知:•GAS5参与调节患有IBD的儿科患者的肠MMP-2和MMP-9;•GAS5-AS1从未在IBD的背景下进行过研究;•GAS5-AS1调节GAS5的表达,增加其在癌症的组织和体外细胞模型中的稳定性。新增内容:•GAS5-AS1与GAS5和IBD临床参数相关;•GAS5-AS1可以调节巨噬细胞中的GAS5水平;•GAS5-AS1可以用作潜在的IBD诊断生物标志物。
