miR-122主要是在肝细胞中发现的，在肝细胞中，它是最为丰富的microRNA，并且在调节体内胆固醇方面发挥着主要作用。然而，在一些患有肝细胞癌的病人体内。这种microRNA丢失导致预后不良(poor prognosis)。在一项新的动物研究中，来自美国俄亥俄州立大学综合癌症中心的研究人员发现肝细胞中一种被称作miR-122的microRNA(miR)丢失可能导致肝癌产生，而且恢复这种分子可能延缓肿瘤生长，从而一种新的方法来治疗这种疾病。相关研究结果发表在Journal of Clinical Investigation期刊上。
研究人员研究了当肝细胞缺乏一种被称作microRNA-122(miR-122)的分子时会发生什么。他们发现当这种分子丢失时，肝脏产生脂肪沉积、炎症和类似肝细胞癌(hepatocellular carcinoma, HCC)的肿瘤，其中肝细胞癌是一种最为常见形式的肝癌。
当研究人员通过将miR-122基因导入肝细胞来人工恢复miR-122到接近正常水平，它能够显著性地降低肿瘤的大小和数量：在经过处理的动物体内，肿瘤占肝脏平均表面积的8%，而在未接受处理的对照动物体内，肿瘤所占比例为40%。
这些发现揭示miR-122在健康肝脏中发挥着至关重要的肿瘤抑制性作用，而且对一些患有肝癌的病人而言，这也可能着重强调了加入miR-122所发挥的治疗性作用。(生物谷：Bioon.com)
本文编译自Loss of Tiny Liver Molecule Might Lead to Liver Cancer
doi: 10.1172/JCI63539
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Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver
1.Shu-hao Hsu, Bo Wang, Janaiah Kota, Jianhua Yu, Stefan Costinean, Huban Kutay, Lianbo Yu, Shoumei Bai, Krista La Perle, Raghu R. Chivukula, Hsiaoyin Mao, Min Wei, K. Reed Clark, Jerry R. Mendell, Michael A. Caligiuri, Samson T. Jacob, Joshua T. Mendell, Kalpana Ghoshal
miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, delivery of miR-122 to a MYC-driven mouse model of HCC strongly inhibited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.
