State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, PR China.
Oncol Rep. 2011 May;25(5):1353-63. doi: 10.3892/or.2011.1204. Epub 2011 Mar 3.
Nasopharyngeal carcinoma (NPC) is posing a serious health problem worldwide. The association between its pathogenesis and microRNAs (miRNA) has not been elucidated. In this study, miRNA expression profiling was performed to screen the miRNA expression changes in 8 NPC tissues and 4 normal nasopharyngeal tissues. Thirty-four miRNAs were identified to be differentially expressed; of these, one miRNA (miR-18a) was overexpressed and 33 miRNAs (miR-34b, miR-34c, let-7 family, etc.) were underexpressed in NPC tissues compared to the normal samples. Validation was performed by real-time quantitative PCR for two altered miRNAs (miR-34b and let-7g) and one non-differentially expressed miRNA (miR-30c). Unsupervised hierarchical clustering analysis showed that the aberrant miRNAs were correlated with the clinical stage of NPC patients. In addition to several biological pathways that are well characterised in NPC and which were significantly targeted by the underexpressed miRNAs, two novel pathways, nervous system development and sensory perception of sound, were identified to be strongly associated with NPC development. Furthermore, a c-Myc centered miRNA regulatory network was inferred in NPC. Our study reveals that aberrantly expressed miRNAs play important roles in NPC tumorigenesis and may serve as potential targets for novel therapeutic strategies in the future.
鼻咽癌(NPC)是全球面临的严重健康问题。其发病机制与 microRNAs(miRNA)的关系尚未阐明。本研究通过 miRNA 表达谱分析筛选了 8 例 NPC 组织和 4 例正常鼻咽组织中的 miRNA 表达变化。鉴定出 34 个 miRNA 存在差异表达;其中,miR-18a 过表达,miR-34b、miR-34c、let-7 家族等 33 个 miRNA 在 NPC 组织中表达下调,与正常样本相比。通过实时定量 PCR 对两个改变的 miRNA(miR-34b 和 let-7g)和一个非差异表达的 miRNA(miR-30c)进行了验证。无监督层次聚类分析显示,这些异常 miRNA 与 NPC 患者的临床分期相关。除了 NPC 中已经明确的几个被下调 miRNA 显著靶向的生物学途径外,还确定了两个新的途径,神经系统发育和声音感觉感知,与 NPC 发展密切相关。此外,还推断出 NPC 中存在一个以 c-Myc 为中心的 miRNA 调控网络。我们的研究表明,异常表达的 miRNA 在 NPC 肿瘤发生中发挥重要作用,可能成为未来新的治疗策略的潜在靶点。