Geisinger Commonwealth School of Medicine, Scranton, PA, USA.
Topiwala National Medical College, Mumbai, India.
J Cell Mol Med. 2018 Apr;22(4):2071-2085. doi: 10.1111/jcmm.13553. Epub 2018 Feb 7.
Hepatitis C virus (HCV) infection is a serious worldwide healthcare issue. Its association with various liver diseases including hepatocellular carcinoma (HCC) is well studied. However, the study on the relationship between HCV infection and the development of insulin resistance and diabetes is very limited. Current research has already elucidated some underlying mechanisms, especially on the regulation of metabolism and insulin signalling by viral proteins. More studies have emerged recently on the correlation between HCV infection-derived miRNAs and diabetes and insulin resistance. However, no studies have been carried out to directly address if these miRNAs, especially circulating miRNAs, have causal effects on the development of insulin resistance and diabetes. Here, we proposed a new perspective that circulating miRNAs can perform regulatory functions to modulate gene expression in peripheral tissues leading to insulin resistance and diabetes, rather than just a passive factor associated with these pathological processes. The detailed rationales were elaborated through comprehensive literature review and bioinformatic analyses. miR-122 was identified to be one of the most potential circulating miRNAs to cause insulin resistance. This result along with the idea about the driver function of circulating miRNAs will promote further investigations that eventually lead to the development of novel strategies to treat HCV infection-associated extrahepatic comorbidities.
丙型肝炎病毒（HCV）感染是一个严重的全球医疗保健问题。其与包括肝细胞癌（HCC）在内的各种肝脏疾病的关联已得到充分研究。然而，关于 HCV 感染与胰岛素抵抗和糖尿病发展之间关系的研究非常有限。目前的研究已经阐明了一些潜在的机制，特别是病毒蛋白对代谢和胰岛素信号的调节。最近出现了更多关于 HCV 感染衍生的 microRNA 与糖尿病和胰岛素抵抗之间相关性的研究。然而，尚无研究直接解决这些 microRNA，特别是循环 microRNA 是否对胰岛素抵抗和糖尿病的发展具有因果作用。在这里，我们提出了一个新的观点，即循环 microRNA 可以发挥调节功能，在周围组织中调节基因表达，从而导致胰岛素抵抗和糖尿病，而不仅仅是与这些病理过程相关的被动因素。通过全面的文献回顾和生物信息学分析，详细阐述了其合理依据。miR-122 被确定为最有可能导致胰岛素抵抗的循环 microRNA 之一。这一结果以及关于循环 microRNA 驱动功能的想法，将促进进一步的研究，最终导致开发治疗 HCV 感染相关肝外合并症的新策略。
