The next thing in prognostic molecular markers: microRNA signatures of cancer.
The next thing in prognostic molecular markers: microRNA signatures of cancer.
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DOI：
10.1136/gut.2009.200022
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发表时间：
2010-06
期刊：
影响因子：
24.5
通讯作者：
Tewari M
中科院分区：
文献类型：
--
作者：
Grady WM;Tewari M
已知癌症是癌基因和肿瘤抑制基因的突变和表观遗传学改变累积的结果，它们共同导致正常细胞转化为癌细胞。因此，癌细胞的临床行为已被逻辑地预测为反映这些突变和改变的基因的结果。这一假设带来了这样的希望：基因活性或表达的测量可以用作生物标志物，以准确确定哪些肿瘤会复发，哪些可能对特定治疗有反应。因此，30多年来，一直在寻找能够准确预测肿瘤复发风险和对化疗反应的行为的突变或改变的基因。在Gut杂志5月号上，Li等人报道了一种微小RNA基因表达特征的发现，该特征显示了用于确定胃癌个体预后的相当大的希望。[1]他们对这组胃癌预后微小RNA得鉴定是最近几项研究之一，这些研究发现这类小得非编码RNA可用于预测多种不同癌症得行为，包括急性髓细胞白血病，慢性淋巴细胞白血病，结肠癌，胰腺癌与非小细胞肺癌. 2这些报道强调了这类相对较新鉴定的RNA分子显示出作为癌症诊断和预后生物标志物的巨大潜力。除了微小RNA作为癌症早期检测和管理的候选生物标志物的前景之外，对于将微小RNA用作新型治疗靶点和作为用于治疗癌症的全新治疗剂的用途也存在相当大的兴奋。RNA和微小RNA为了了解我们对微小RNA在细胞生理学和疾病方面的理解，把它们放在我们目前对细胞分子生物学中RNA和DNA的理解的背景下是很重要的。RNA作为将DNA序列编码翻译成蛋白质的信使的作用已经被理解了几十年，并且是信使RNA的典型功能。已经发现的RNA的其他功能包括鉴定核酶和具有结构作用的RNA种类。在过去的十年中，我们已经认识到，除了信使RNA、核酶和结构RNA之外，还有一类称为microRNA的小RNA分子，它们代表基因调控网络的重要层，传统上已知基因调控网络包括转录因子、调节mRNA稳定性的蛋白质、调节mRNA翻译成蛋白质的蛋白质、和控制蛋白质降解的因子。值得注意的是，microRNAs可以调节大多数多细胞生物体中几乎所有基因的表达水平，并且似乎提供了调节细胞中mRNA和蛋白质水平的手段。[3] 2006年诺贝尔生理学或医学奖授予Andrew Z. Fire和CraigC.梅洛，他进行了一些开创性的研究，确定了miRNAs和其他小RNAs对基因调控的影响。4
Cancer is known to be a consequence of the accumulation of mutations and epigenetic alterations of oncogenes and tumour suppressor genes, which cooperate to cause a normal cell to transform into a cancer cell. Thus, the clinical behaviour of cancer cells has been logically predicted to reflect the consequences of these mutated and altered genes. This hypothesis has led to the hope that measurement of gene activity or expression can be used as biomarkers to accurately determine which tumours will recur and which are likely to respond to specific treatments. Consequently, for over three decades, there has been an ongoing search to identify mutated or otherwise altered genes that can precisely predict the behaviour of tumours with regards to risk for recurrence and response to chemotherapy. In the May issue of Gut, Li et al reported on the discovery of a microRNA gene expression signature that shows considerable promise for determining the prognosis of individuals with gastric cancer. 1 Their identification of this panel of prognostic microRNAs for gastric cancer is one of several recent studies that have found this class of small non-coding RNAs to be useful for predicting the behaviour of a variety of different cancers, including acute myeloid leukaemia, chronic lymphocytic leukaemia, colon cancer, pancreatic cancer, and nonsmall cell lung cancer. 2 These reports highlight that this relatively newly identified class of RNA molecules is showing substantial potential to be used as diagnostic and prognostic biomarkers for cancer. Beyond the promise that microRNAs hold as candidate biomarkers for the early detection and management of cancer, there is also considerable excitement for the use of miRNAs as a novel class of therapeutic targets and as an entirely new class of therapeutic agents for the treatment of cancers.RNA AND MICRORNA In order to appreciate where our understanding of microRNAs is with regards to cell physiology and disease, it is important to place them in the context of our current understanding of RNA and DNA in the molecular biology of the cell. The role of RNA as a messenger for translating DNA sequence code into proteins has been understood for decades and is a canonical function of messenger RNA. Additional functions of RNA that have been discovered include the identification of ribozymes and RNA species with structural roles. Over the last decade, we have come to appreciate that, in addition to messenger RNAs, ribozymes and structural RNAs, there is a class of small RNA molecules, called microRNAs, that represent an important layer of the gene regulation network, which traditionally has been known to include transcription factors, proteins that regulate mRNA stability, proteins that regulate the translation of mRNA into protein, and factors that control protein degradation. Remarkably, microRNAs may regulate the expression levels of nearly all genes in most multicellular organisms, and appear to provide a means for modulating the mRNA and proteins levels in cells. 3 The profound significance of microRNAs and the process of gene expression regulation by small RNAs (also known as ‘RNA interference’) in biology was recognised in 2006 by the award of the Nobel Prize in Physiology or Medicine to Andrew Z. Fire and Craig C. Mello, who carried out some of the seminal studies that defined the effect of miRNAs and other small RNAs on gene regulation. 4
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DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
2009-04-01
影响因子：
4.1
作者：
Guo, Junming;Miao, Ying;Wang, Yanjun
通讯作者：
Wang, Yanjun
影响因子：
9.7
作者：
Che, XM;Hokita, S;Aikou, T
通讯作者：
Aikou, T
影响因子：
120.7
作者：
Schetter, Aaron J.;Leung, Suet Yi;Harris, Curtis C.
通讯作者：
Harris, Curtis C.
影响因子：
3.3
作者：
Resnick, MB;Gavilanez, M;Moss, SF
通讯作者：
Moss, SF
影响因子：
37.3
作者：
Lanza G;Ferracin M;Gafà R;Veronese A;Spizzo R;Pichiorri F;Liu CG;Calin GA;Croce CM;Negrini M
通讯作者：
Negrini M