Modern diets, which often feature high levels of fat and charcoal-grilled meat, contribute to the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD), resulting in liver cancer progression. Benzo(a)pyrene (B[a]P) is a common environmental and foodborne pollutant found in smoke and fire-grilled foods, which can have an adverse effect on human health. Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer and the second leading cause of cancer-related deaths worldwide. The epidemiological studies suggest that both environmental risk factors and chronic liver injury including NAFL are important for HCC development, but the precise mechanisms linking eating habits to hepato-carcinogenesis remain unclear. In the present study, we demonstrated that various miRNAs in B[a]P-exposed tumor cells contribute to tumor metastasis, among which miR-650 could be the most potent inducer. Furthermore, we found that the suppressor of cytokine signaling 3 (SOCS3) is directly regulated by miR-650 and its suppression regulates the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) cascade. Our findings reveal a possible adverse outcome pathway of SOCS3/JAK/STAT3 regulation in B[a]P-induced HCC progress. These results provide a better understanding of the adverse effects of chronic exposure to B[a]P on human health.

中文翻译：

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苯并[a]芘通过SOCS3/JAK/STAT3级联刺激miR-650表达促进脂肪肝和肝细胞癌的发病机制


现代饮食通常含有高水平的脂肪和炭烤肉，会导致肥胖和非酒精性脂肪肝 (NAFLD) 的发病机制，从而导致肝癌进展。苯并(a)芘 (B[a]P) 是一种常见的环境和食源性污染物，存在于烟雾和火烤食品中，对人类健康产生不利影响。肝细胞癌（HCC）是全球第五大癌症原因，也是全球癌症相关死亡的第二大原因。流行病学研究表明，环境危险因素和包括NAFL在内的慢性肝损伤对HCC的发展很重要，但饮食习惯与肝癌发生之间的确切机制仍不清楚。在本研究中，我们证明暴露于 B[a]P 的肿瘤细胞中的多种 miRNA 有助于肿瘤转移，其中 miR-650 可能是最有效的诱导剂。此外，我们发现细胞因子信号传导抑制因子 3 (SOCS3) 直接受 miR-650 调节，其抑制调节 Janus 激酶/信号转导器和转录激活因子 3 (JAK/STAT3) 级联的激活。我们的研究结果揭示了 SOCS3/JAK/STAT3 调节在 B[a]P 诱导的 HCC 进展中可能存在的不良后果途径。这些结果使人们更好地了解长期接触 B[a]P 对人类健康的不利影响。