Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
Cancer Biol Ther. 2010 Mar 15;9(6):446-52. doi: 10.4161/cbt.9.6.10894. Epub 2010 Mar 8.
The discovery of microRNAs (miRNAs) has opened a new avenue for both diagnosis and treatment of cancers. Accumulating experimental evidences indicate that miRNAs are aberrantly expressed in different tumor types and have a critical role in tumorigenesis. However, the miRNA expression profile in neuroblastoma (NB), one of the most common cancer forms in children, has not been well characterized. In the present study, we established a heterotopic transplant mice model of NB and employed miRNA microarray analysis to identify miRNAs that are differentially expressed in metastatic NB compared to primary NB. A list of 54 miRNAs was found to be significantly altered in metastatic tumors compared to primary tumors. These differentially-expressed miRNAs were selectively validated by a stem-loop qRT-PCR assay. Furthermore, we predicted a list of potential miRNA-target pairs that may be involved in the metastasis of neuroblastoma by three different computer-aided algorithms. Taken together, our results indicate that a unique panel of miRNAs are associated with metastatic NB and these differentially-expressed miRNAs may play an important role in the NB metastatic process. This finding may also shed light in our understanding of the nature of metastatic NB and provide a potential novel target for therapeutic treatment of this tumor.
微小 RNA(miRNAs)的发现为癌症的诊断和治疗开辟了新途径。越来越多的实验证据表明,miRNAs 在不同类型的肿瘤中异常表达,在肿瘤发生中起关键作用。然而,神经母细胞瘤(NB)的 miRNA 表达谱尚未得到很好的描述,NB 是儿童中最常见的癌症类型之一。在本研究中,我们建立了 NB 的异位移植小鼠模型,并采用 miRNA 微阵列分析来鉴定与原发性 NB 相比在转移性 NB 中差异表达的 miRNAs。与原发性肿瘤相比,在转移性肿瘤中发现有 54 个 miRNAs 显著改变。通过茎环 qRT-PCR 检测对这些差异表达的 miRNAs 进行了选择性验证。此外,我们通过三种不同的计算机辅助算法预测了一组可能参与神经母细胞瘤转移的潜在 miRNA 靶对。总之,我们的结果表明,一组独特的 miRNAs 与转移性 NB 相关,这些差异表达的 miRNAs 可能在 NB 的转移过程中发挥重要作用。这一发现也可能使我们对转移性 NB 的本质有更深入的了解,并为该肿瘤的治疗提供一个新的潜在靶点。