Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1-98, 3-Chome, Kasugade-Naka, Konohana-ku, Osaka 554-8558, Japan.
Toxicol Lett. 2011 Jan 15;200(1-2):46-52. doi: 10.1016/j.toxlet.2010.10.013. Epub 2010 Oct 28.
MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level, are believed promising biomarkers for several diseases as well as a novel target of drugs, including cancer. In particular, miRNAs might allow detection of early stages of carcinogenesis. The present study was conducted to provide concrete evidence using chemical-induced hepatocarcinogenesis in rat as a model. We thereby observed aberrant fluctuation of circulating miRNAs in the serum of rats not only with neoplastic lesions such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), but also with preneoplastic lesions, such as foci of hepatocellular alteration (FHA). Additional qRT-PCR analysis revealed gradual elevation of some circulating miRNAs (i.e., let-7a, let-7f, miR-34a, miR-98, miR-331, miR-338 and miR-652) with progress of hepatocarcinogenesis. Interestingly, increased levels of let-7a, let-7f and miR-98 were statistically significant even in the serum of rats at very early stages. These findings provide the first evidences that circulating miRNAs have the potential to predict carcinogenesis at earlier stages, preneoplastic lesions than with previous biomarkers and that they might be utilized to monitor the progress of tumor development.
微小 RNA（miRNAs）是一类小的非编码 RNA，可在转录后水平调节基因表达，被认为是多种疾病的有前途的生物标志物，也是包括癌症在内的药物的新靶点。特别是，miRNAs 可能允许检测癌发生的早期阶段。本研究旨在使用化学诱导的大鼠肝癌发生作为模型提供具体证据。因此，我们不仅在具有肿瘤病变（如肝细胞腺瘤（HCA）和肝细胞癌（HCC））的大鼠血清中观察到循环 miRNAs 的异常波动，而且在具有癌前病变（如肝细胞改变灶（FHA））的大鼠血清中也观察到循环 miRNAs 的异常波动。额外的 qRT-PCR 分析显示，随着肝癌发生的进展，一些循环 miRNAs（即 let-7a、let-7f、miR-34a、miR-98、miR-331、miR-338 和 miR-652）逐渐升高。有趣的是，即使在肝癌发生的早期阶段，let-7a、let-7f 和 miR-98 的水平升高也具有统计学意义。这些发现提供了第一个证据，即循环 miRNAs 有可能在更早阶段预测癌发生，预测癌前病变比以前的生物标志物更准确，并且它们可能用于监测肿瘤发展的进展。
