慢性炎症被广泛认为是促进和恶化恶性肿瘤发展的重要因素，包括肝细胞癌。本研究旨在探究微小RNA在与炎症相关的难治性肝癌发生中的潜在作用。通过对不同病因动物模型肝癌中改变的微小RNA进行全面分析，我们发现在肝炎相关肝癌动物的肝脏中，miR-122是最显著下调的微小RNA。虽然先前的研究已经指出了miR-122在维持肝细胞功能方面的重要性，但其在基础疾病中充当的具体角色仍不清楚，是触发器还是潜在疾病后果。通过对动物和体外模型的广泛分析，我们成功地证明了miR-122的转录受免疫调节细胞因子、转化生长因子-beta 1（TGFβ1）和骨形态发生蛋白-6（BMP6）的差异调控。此外，我们提供了有力的证据，直接将降低的miR-122转录与慢性炎症和慢性肝病联系起来。本研究结果强烈暗示，长期激活促炎信号通路，导致细胞因子介导的miR-122调控紊乱，可能显著促进慢性肝病的发病和恶化。

Chronic inflammation is widely recognized as a significant factor that promotes and worsens the development of malignancies, including hepatocellular carcinoma. This study aimed to explore the potential role of microRNAs in inflammation-associated nonresolving hepatocarcinogenesis. By conducting a comprehensive analysis of altered microRNAs in animal models with liver cancer of various etiologies, we identified miR-122 as the most significantly downregulated microRNA in the liver of animals with inflammation-associated liver cancer. Although previous research has indicated the importance of miR-122 in maintaining hepatocyte function, its specific role as either the trigger or the consequence of underlying diseases remains unclear. Through extensive analysis of animals and in vitro models, we have successfully demonstrated that miR-122 transcription is differentially regulated by the immunoregulatory cytokines, by the transforming growth factor-beta 1 (TGFβ1), and the bone morphogenetic protein-6 (BMP6). Furthermore, we presented convincing evidence directly linking reduced miR-122 transcription to inflammation and in chronic liver diseases. The results of this study strongly suggest that prolonged activation of pro-inflammatory signaling pathways, leading to disruption of cytokine-mediated regulation of miR-122, may significantly contribute to the onset and exacerbation of chronic liver disease.