Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Clin Cancer Res. 2012 Aug 15;18(16):4234-9. doi: 10.1158/1078-0432.CCR-11-2010. Epub 2012 Jun 18.
MicroRNAs (miRNA) are approximately 18 to 25 nucleotides in length and affect gene expression by silencing the translation of messenger RNAs. Because each miRNA regulates the expression of hundreds of different genes, miRNAs can function as master coordinators, efficiently regulating and coordinating multiple cellular pathways and processes. By coordinating the expression of multiple genes, miRNAs are responsible for fine-tuning the cell's most important processes, like the ones involved in cellular growth and proliferation. Dysregulation of miRNAs appears to play a fundamental role in the onset, progression and dissemination of many cancers, and replacement of downregulated miRNAs in tumor cells results in a positive therapeutic response. Thus, in theory, inhibition of a particular miRNA linked to cancer onset or progression can remove the inhibition of the translation of a therapeutic protein-and conversely, administration of a miRNA mimetic can boost the endogenous miRNA population repressing the translation of an oncogenic protein. Although several basic questions about their biologic principles still remain to be answered, and despite the fact that all data with respect to miRNAs and therapy are still at the preclinical level, many specific characteristics of miRNAs in combination with compelling therapeutic efficacy data have triggered the research community to start exploring the possibilities of using miRNAs as potential therapeutic candidates.
微 RNA(miRNA)的长度约为 18 到 25 个核苷酸,通过沉默信使 RNA 的翻译来影响基因表达。因为每个 miRNA 可以调控数百个不同基因的表达,所以 miRNA 可以作为主控协调因子,有效地调控和协调多个细胞途径和过程。通过协调多个基因的表达,miRNA 负责微调细胞最重要的过程,如涉及细胞生长和增殖的过程。miRNA 的失调似乎在许多癌症的发生、进展和扩散中起着根本作用,在肿瘤细胞中替代下调的 miRNA 会导致积极的治疗反应。因此,理论上,抑制与癌症发生或进展相关的特定 miRNA 可以消除对治疗蛋白翻译的抑制——相反,给予 miRNA 模拟物可以增强内源性 miRNA 群体,抑制致癌蛋白的翻译。尽管关于它们的生物学原理还有一些基本问题仍有待回答,而且尽管所有关于 miRNA 和治疗的信息仍处于临床前水平,但 miRNA 的许多特定特征结合令人信服的治疗效果数据,促使研究界开始探索将 miRNA 用作潜在治疗候选物的可能性。