Inflammatory bowel disease (IBD) is mostly responsible for the development of colitis-associated colon cancer. Of the several signaling pathways involved in colonic inflammation, the activation and crosstalk between NF-κB and STAT3 serve as the pivotal regulatory hubs that regulate epithelial tumorigenesis by linking inflammation with cancer development. Understanding the molecular mechanisms regulating the crosstalk between NF-κB and STAT3 will help in targeting these signaling pathways and halt epithelial tumorigenesis. MicroRNAs (miRNAs) play important role in the regulation of NF-κB and STAT3 and function in a positive- or negative feedback loop to regulate the crosstalk of these transcription factor. In the present study we evaluated the aberrant expression of a selected panel of miRNAs (miR-181b, miR-31, miR-34a, miR-146b, miR-221, and miR-155) that regulate the crosstalk between NF-κB and STAT3 during colitis-associated tumorigenesis. We used the stepwise colorectal carcinogenesis murine model known as Azoxymethane (AOM)/Dextran sodium sulphate (DSS) to recapitulate the different stages of tumorigenesis. Our results revealed that the expression of the selected miRNAs changed dynamically in a stepwise pattern as colonic tissue transforms from normal to actively inflamed to neoplastic state, in accordance with the gradual activation of NF-κB and STAT3, suggesting that the aberrant expression of these miRNAs could function as the epigenetic switch between inflammation and colorectal tumorigenesis. We were able to elucidate the contribution of miRNAs in the NF-κB - STAT3 crosstalk during the stepwise development of colitis-associated carcinoma, and this could improve our understanding of the molecular pathology of colorectal tumorigenesis and even suggesting a therapeutic strategy by modulating the expression of these regulating miRNAs.

中文翻译：

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结肠炎相关肿瘤发生过程中调节NF-κB和STAT3串扰的miRNA的差异表达。

炎症性肠病（IBD）主要与结肠炎相关的结肠癌的发展有关。在涉及结肠炎症的几种信号通路中，NF-κB和STAT3之间的激活和串扰是通过将炎症与癌症发展联系起来调节上皮肿瘤发生的关键调节中心。了解调节NF-κB和STAT3之间的串扰的分子机制将有助于靶向这些信号通路并阻止上皮肿瘤发生。MicroRNA（miRNA）在调节NF-κB和STAT3中起重要作用，并在正或负反馈回路中调节这些转录因子的串扰。在本研究中，我们评估了一组选定的miRNA（miR-181b，miR-31，miR-34a，miR-146b，miR-221，和miR-155）在结肠炎相关的肿瘤发生过程中调节NF-κB和STAT3之间的串扰。我们使用逐步的结直肠癌发生鼠模型，称为Azoxymethane（AOM）/ Dextran硫酸钠（DSS）来概括肿瘤发生的不同阶段。我们的研究结果表明，随着NF-κB和STAT3的逐渐激活，当结肠组织从正常状态转变为主动发炎性状态时，所选miRNA的表达会以逐步的方式动态变化，这提示这些miRNA的异常表达可以作为炎症和结直肠肿瘤发生之间的表观遗传转换。我们能够阐明在结肠炎相关癌的逐步发展过程中，miRNA在NF-κB-STAT3串扰中的作用，