Haldar Subrata, Basu Aruna
Dept of Pharmacology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.
Mol Cell Pharmacol. 2011 Jan 1;3(3):135-141.
The disorder of microRNAs (miRNAs) often referred as 'micromanagers of gene expression' has been implicated with a vast array of neoplasmthe discovery establishes an important connection with the etiology, diagnosis and potential therapy of human cancer. Indeed, the wide range of profiling studies enabled to create miRNA signatures of solid tumors as well as cancers of blood origin. MiRNAs have been observed to play a significant role in the regulation of gene expression-a critical aspect of many biological processes, including cell development, differentiation, apoptosis and proliferation. The differential expression levels of miRNAs in tumors and their normal counterpart have enabled scientists to designate their roles as oncomir or tumor suppressor. Interestingly, the diminishment of oncogenic or enhanced levels of tumor suppressor miRNAs (antagomirs) have been reported to modulate the sensitivity of cancer cells to anticancer agents. To the other end, carcinogenic chemicals either possess the ability of silencing beneficial tumor suppressive miRNAs or maintain the augmented levels of their oncogenic counterpart. In this article we provide a comprehensive overview on the modulation of these "micromanaging oligos" by cancer causing as well as cancer preventing agents.
微小RNA(miRNA)的失调常被称为“基因表达的微观管理者”,与大量肿瘤有关。这一发现建立了与人类癌症病因、诊断和潜在治疗的重要联系。事实上,广泛的分析研究能够创建实体瘤以及血液起源癌症的miRNA特征。人们观察到miRNA在基因表达调控中发挥着重要作用,而基因表达调控是许多生物过程的关键方面,包括细胞发育、分化、凋亡和增殖。肿瘤与其正常对应物中miRNA的差异表达水平使科学家们能够将它们的作用指定为癌基因miRNA或肿瘤抑制因子。有趣的是,据报道,致癌性miRNA水平的降低或肿瘤抑制性miRNA(抗miR)水平的升高可调节癌细胞对抗癌药物的敏感性。另一方面,致癌化学物质要么具有沉默有益的肿瘤抑制性miRNA的能力,要么维持其致癌对应物的升高水平。在本文中,我们全面概述了致癌剂和防癌剂对这些“微观管理寡核苷酸”的调节作用。