Start Up Unit, Department of Experimental Oncology, Fondazione IRCCS, Istituto Nazionale Tumori, Milano, Italy.
Carcinogenesis. 2012 Jun;33(6):1126-33. doi: 10.1093/carcin/bgs140. Epub 2012 Apr 3.
When, ∼20 years ago, investigators first determined that components of the genome considered nonfunctional had, in fact, gene regulatory capacity, they probably had no idea of their potential in controlling cell fate and were forced to revise and somehow reorganize their view of the molecular biology. Indeed, it is currently well documented how a class of small non-coding RNAs, microRNAs, are conserved among the species, expressed in different tissues and cell types and involved in almost every biological process, including cell cycle, growth, apoptosis, differentiation and stress response, exerting a finely tuned regulation of gene expression by targeting multiple molecules. As a consequence of the widespread range of processes they are able to influence, it is not surprising that miRNA deregulation is a hallmark of several pathological conditions, including cancer. Indeed, the aberrant expression of these tiny molecules in human tumors is not just a casual association, but they can exert a causal role, as oncogenes or tumor suppressors, in different steps of the tumorigenic process, from initiation and development to progression toward the acquisition of a metastatic phenotype. An increasing body of evidence has indeed proved the importance of miRNAs in cancer, suggesting their possible use as diagnostic, prognostic and predictive biomarkers and leading to exploit miRNA-based anticancer therapies, either alone or in combination with current targeted therapies, with the goal to improve disease response and increase cure rates. Here, we review our current knowledge about miRNA involvement in cancer.
大约 20 年前,当研究人员首次确定被认为是非功能的基因组成分实际上具有基因调控能力时,他们可能不知道它们在控制细胞命运方面的潜力,因此被迫修改并以某种方式重新组织他们对分子生物学的看法。事实上,目前有大量文献记录了一类小的非编码 RNA,即 microRNAs,在物种间是如何保守的,它们在不同的组织和细胞类型中表达,并参与几乎所有的生物学过程,包括细胞周期、生长、凋亡、分化和应激反应,通过靶向多个分子对基因表达进行精细调控。由于它们能够影响的过程范围广泛,miRNA 失调是几种病理状况(包括癌症)的标志也就不足为奇了。事实上,这些微小分子在人类肿瘤中的异常表达不仅仅是一种偶然的关联,而是它们可以在肿瘤发生过程的不同阶段发挥致癌基因或肿瘤抑制基因的因果作用,从起始和发展到获得转移表型。越来越多的证据确实证明了 miRNAs 在癌症中的重要性,表明它们可能作为诊断、预后和预测生物标志物,并导致 miRNA 为基础的抗癌疗法的开发,无论是单独使用还是与现有的靶向治疗联合使用,目的是提高疾病反应率并提高治愈率。在这里,我们回顾了我们目前对 miRNA 在癌症中的参与的了解。