文章：

人类癌症中的MicroRNA特征

MicroRNA signatures in human cancers

原文发布日期：2006-11-01

DOI: 10.1038/nrc1997

类型: Review Article

开放获取: 否

要点：

1. MicroRNAs (miRNAs) located in genomic regions amplified in cancers (such as the miR-17–92 cluster) function as oncogenes, whereas miRNAs located in portions of chromosomes deleted in cancers (such as the miR-15a–miR-16-1 cluster) function as tumour suppressors.
2. Abnormal expression of miRNAs has been found in both solid and haematopoietic tumours by various genome-wide techniques (including different microarray platforms or bead-based flow cytometry).
3. The abnormally expressed miRNAs in human cancers target transcripts of essential protein-coding genes involved in tumorigenesis, such as the Ras oncogenes by let-7 family members, the BCL2 anti-apoptotic gene by the miR-15a–miR-16-1 cluster, the E2F1 transcription factor by the miR-17–92 cluster or the BCL6 anti-apoptotic gene by miR-127.
4. MiRNA expression fingerprints correlate with clinical and biological characteristics of tumours, including tissue type, differentiation, aggression and response to therapy.
5. The fact that consistent abnormal expression of the precursor miRNA, but not of the correspondent active molecule, is found in various types of cancers, raises the possibility that the 'non-active' part of the miRNA molecule could have 'independent' and as yet unknown functions that could be important in tumorigenesis.
6. Germline sequence abnormalities were identified in miRNA genes and transcripts, and in targeted sequences in messenger RNAs that are known to be targets of miRNAs. Furthermore, as each miRNA has many targets, inherited minor variations in miRNA expression could have important consequences for the expression of various protein-coding genes involved in malignant transformation. Therefore, it is tempting to propose that both these phenomenons are involved in familial predisposition to cancer.

要点翻译：

1. 位于癌症基因组扩增区域（如miR-17-92基因簇）的microRNAs（miRNAs）发挥癌基因功能，而定位于癌症染色体缺失区段（如miR-15a–miR-16-1基因簇）的miRNAs则具有肿瘤抑制因子作用。
2. 通过多种全基因组技术（包括不同微阵列平台或基于微珠的流式细胞术），在实体瘤和造血系统肿瘤中均发现miRNAs的异常表达。
3. 人类癌症中异常表达的miRNAs靶向参与肿瘤发生的关键蛋白编码基因转录本，例如let-7家族成员靶向Ras癌基因，miR-15a–miR-16-1基因簇靶向BCL2抗凋亡基因，miR-17-92基因簇靶向E2F1转录因子，以及miR-127靶向BCL6抗凋亡基因。
4. miRNA表达谱与肿瘤的临床及生物学特征相关，包括组织类型、分化程度、侵袭性和治疗反应。
5. 在不同类型癌症中持续存在前体miRNA（而非其对应的活性分子）的异常表达，这提示miRNA分子的“非活性”部分可能具有“独立”且尚未知的功能，这些功能可能在肿瘤发生中起重要作用。
6. 研究已在miRNA基因及其转录本、以及已知miRNA靶标信使RNA的靶向序列中鉴定出种系序列异常。此外，由于每个miRNA具有多个靶标，miRNA表达的遗传性微小变异可能对参与恶性转化的多种蛋白编码基因表达产生重要影响。因此，有理由认为这两种现象均参与癌症的家族易感性。

英文摘要：

MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.

摘要翻译： 

微小RNA（miRNA）的改变参与了人类癌症的发生和进展。与正常细胞相比，miRNA基因在恶性肿瘤中广泛差异表达的原因可以归结为这些基因位于癌症相关的基因组区域、表观遗传机制以及miRNA加工过程的改变。对人类肿瘤进行miRNA表达谱分析，已发现与诊断、分期、进展、预后及治疗反应相关的特征。此外，表达谱还被用于识别可能代表活化致癌通路下游靶点的miRNA基因，或靶向参与癌症的蛋白编码基因的miRNA。

原文链接：

MicroRNA signatures in human cancers