Division of Gastroenterology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Inflamm Bowel Dis. 2019 Jan 1;25(1):78-84. doi: 10.1093/ibd/izy279.
MicroRNAs (miRNAs) are important post-translational regulators. Elevated levels of miR-206 in ulcerative colitis (UC) were associated with suppression of anti-inflammatory A3 adenosine receptor (A3AR) expression. However, the relationship of miR-206 to histologic remission in UC patients remains unknown. This study correlates expression levels of miR-206 with histologic remission in patients treated via long-term mesalamine treatment to identify a possible mode of action for this mainstay drug for UC.
Expression of miR-206 and its target A3AR were analyzed in HT29 cell line before and after mesalamine treatment (2 mM) at different time points (0, 4, 12, and 24 hours) by qRT-PCR and western blot analysis. Expression of miR-206 and pathological scores of colonoscopic biopsy specimens were studied in 10 UC patients treated with mesalamine treatment for 2 to 6 years.
miR-206 transcripts decreased 2.23-fold (P = 0.0001) 4 hours after 2 mM mesalamine treatment in HT29 colon cells compared with untreated controls. However, the mRNA/protein levels of A3AR increased by 4-fold (P = 0.04) and 2-fold, respectively, in same cells. miR-206 relative expression decreased significantly in patients treated with 4.8 g of mesalamine (P = 0.002) but not with 2.4 g (P = 0.35). Tissue assessment of sequential mesalamine-treated colonoscopic biopsies indicate a strong correlation between downregulation of miR-206 and histologic improvement (R = 0.9111).
Mesalamine treatment has an effect on epithelial miRNAs. Downregulation of miR-206 by long-term mesalamine treatment may confer a protective effect in inducing and maintaining histologic remission. Thus, miR-206 expression levels can be utilized as a possible biomarker for therapeutic response to mesalamine treatment.
MicroRNAs (miRNAs) 是重要的翻译后调控因子。溃疡性结肠炎 (UC) 中 miR-206 水平升高与抗炎 A3 腺苷受体 (A3AR) 表达抑制有关。然而，miR-206 与 UC 患者的组织学缓解之间的关系尚不清楚。本研究通过分析长期美沙拉秦治疗的 UC 患者 miR-206 的表达水平与组织学缓解之间的关系，以确定该 UC 主要药物的可能作用机制。
采用 qRT-PCR 和 Western blot 分析在不同时间点 (0、4、12 和 24 小时) 美沙拉秦 (2 mM) 处理前后 HT29 细胞系中 miR-206 的表达及其靶标 A3AR。在接受美沙拉秦治疗 2 至 6 年的 10 例 UC 患者中研究了 miR-206 的表达和结肠镜活检标本的病理评分。
与未处理对照组相比，HT29 结肠细胞在 2 mM 美沙拉秦处理 4 小时后 miR-206 转录物降低了 2.23 倍 (P = 0.0001)。然而，在相同的细胞中，A3AR 的 mRNA/蛋白水平分别增加了 4 倍 (P = 0.04) 和 2 倍。用 4.8 g 美沙拉秦治疗的患者 miR-206 的相对表达明显降低 (P = 0.002)，而用 2.4 g 美沙拉秦治疗的患者则没有 (P = 0.35)。对连续接受美沙拉秦治疗的结肠镜活检组织学评估表明，miR-206 的下调与组织学改善之间存在很强的相关性 (R = 0.9111)。
美沙拉秦治疗对上皮细胞 miRNA 有影响。长期美沙拉秦治疗下调 miR-206 可能在诱导和维持组织学缓解方面发挥保护作用。因此，miR-206 的表达水平可以用作美沙拉秦治疗的治疗反应的可能生物标志物。
