Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that the RNA-binding protein DDX5 binds to the mRNA transcripts of C3 and Fabp1 to augment their expressions posttranscriptionally. Knocking out DDX5 in epithelial cells protected mice from intestinal tumorigenesis and dextran sodium sulfate (DSS)-induced colitis. Identification of DDX5 as a common upstream regulator of tissue-specific oncogenic molecules provides an excellent therapeutic target for intestinal diseases.

中文翻译：

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DDX5 促进癌基因 C3 和 FABP1 表达并驱动肠道炎症和肿瘤发生。


肠道不同部分的肿瘤发生涉及组织特异性致癌驱动因素。在结肠中，补体成分 3 (C3) 激活是炎症和恶性肿瘤的主要原因。相比之下，小肠肿瘤发生涉及脂肪酸结合蛋白 1 (FABP1)。然而，人们对驱动它们在肠道不同部分表达的上游机制知之甚少。在这里，我们报告 RNA 结合蛋白 DDX5 与C3和Fabp1的 mRNA 转录物结合，以增强它们转录后的表达。敲除上皮细胞中的 DDX5 可保护小鼠免受肠道肿瘤发生和葡聚糖硫酸钠 (DSS) 诱导的结肠炎的影响。 DDX5 被鉴定为组织特异性致癌分子的常见上游调节因子，为肠道疾病提供了极好的治疗靶点。