5-氨基水杨酸 (5-ASA) 是维持结肠炎缓解的一线治疗方法。它是一种高效、安全、耐受性良好的药物，具有抗炎和化学预防特性。虽然原发性硬化性胆管炎 (PSC) 合并溃疡性结肠炎患者接受 5-ASA 治疗，但该药物化疗预防作用的分子机制尚不完全清楚。我们之前报道过胆汁酸和脂多糖诱导的 miR-155 表达与 CACO-2 细胞系中错配修复 (MMR) 蛋白的下调相关。因此，在本研究中，进行了一系列体外功能研究，以显示 miR-155 和 5-ASA 预防高微卫星不稳定性 (MSI-H) 之间的表观遗传关系背后的可能机制。在用行为类似内源性 miRNA 的 miR-155Mimic 瞬时转染中，我们在三种人肠上皮细胞系 CACO-2、NCM460D 和 HT-29 中证实了 miR-155 与其靶标 MMR 之间的关系。我们首次证明 5-ASA 可以调节 miR-155 转染细胞中的 MLH1、MSH2、MSH6。这些发现强调，化学保护性 5-ASA 疗法可以有效减弱 miR-155 的表达，并可能预防与 PSC 相关的结直肠癌子集中发生 MSI-H。© 2024。作者。

5-aminosalicylic acid (5-ASA) is a first-line treatment for maintaining colitis remission. It is a highly effective, safe, and well-tolerated drug with anti-inflammatory and chemo-preventive properties. While patients with primary sclerosing cholangitis (PSC) with concomitant ulcerative colitis are treated with 5-ASA, the molecular mechanisms underlying the drug's chemo-preventive effects are not entirely understood. We previously reported that bile acids and lipopolysaccharide-induced miR-155 expression was associated with downregulating mismatch repair (MMR) proteins in CACO-2 cell lines. Therefore, in this investigation, a set of in vitro functional studies was performed to show the possible mechanisms behind the epigenetic relationship between miR-155 and 5-ASA's prevention of high microsatellite instability (MSI-H). In transient transfection with miR-155Mimic, which behaves like endogenous miRNA, we confirmed the relationships between miR-155 and its target MMR in three human intestinal epithelial cell lines: CACO-2, NCM460D and HT-29. We have shown, for the first time, that 5-ASA modulates MLH1, MSH2, MSH6 in miR-155 transfected cells. These findings underline that chemoprotective 5-ASA therapy can effectively attenuate the expression of miR-155 and potentially prevent a development of MSI-H in a subset of colorectal cancers associated with PSC.© 2024. The Author(s).