Jafri Mohammad Alam, Zaidi Syed Kashif, Ansari Shakeel Ahmed, Al-Qahtani Mohammed Hussein, Shay Jerry W
a 1 King Abdulaziz University, Center of Excellence in Genomic Medicine Research , Jeddah, Saudi Arabia.
b 2 UT Southwestern Medical Center, Department of Cell Biology , Dallas, TX, USA +1 214 648 4201 ; +1 214 648 5814 ;
Expert Opin Ther Targets. 2015;19(12):1705-23. doi: 10.1517/14728222.2015.1069816. Epub 2015 Jul 18.
MicroRNAs (miRNAs) are small (19 - 22 nucleotide), non-protein-coding RNA segments that function as master regulators of hundreds of genes simultaneously in both normal and malignant cells. In colorectal cancer (CRC) miRNAs are deregulated and have critical roles in initiation and progression of CRC by interacting with various oncogenes and tumor suppressor genes including APC, KRAS and p53, or by modulating downstream signal transduction pathways. Numerous promising miRNAs have emerged as potential drug targets for therapeutic intervention and possible candidates for replacement therapy in CRC.
In this review the authors summarize the available information on miRNAs and their role in CRC. The authors point out specific miRNAs as potential drug targets and those having a significant role in gene activation and gene silencing during the process of CRC development, to highlight their importance as possible therapeutic candidates for the treatment of CRC.
Targeting miRNAs provides an emerging opportunity to develop effective miRNA-based replacement therapy or antagonists to alter expression in colon cancer patient tumors. However, the biggest challenge is to overcome obstacles associated with pharmacokinetics, delivery and toxicity in order to translate the potential of miRNAs into efficacious anticancer drugs.
微小RNA（miRNA）是小的（19 - 22个核苷酸）非蛋白质编码RNA片段，在正常细胞和恶性细胞中同时作为数百个基因的主要调节因子发挥作用。在结直肠癌（CRC）中，miRNA失调，通过与包括APC、KRAS和p53在内的各种癌基因和肿瘤抑制基因相互作用，或通过调节下游信号转导途径，在CRC的发生和发展中起关键作用。许多有前景的miRNA已成为CRC治疗干预的潜在药物靶点和替代疗法的可能候选者。
在本综述中，作者总结了关于miRNA及其在CRC中作用的现有信息。作者指出特定的miRNA作为潜在的药物靶点，以及那些在CRC发展过程中在基因激活和基因沉默中起重要作用的miRNA，以突出它们作为CRC治疗可能候选者的重要性。
靶向miRNA为开发基于miRNA的有效替代疗法或拮抗剂以改变结肠癌患者肿瘤中的表达提供了一个新的机会。然而，最大的挑战是克服与药代动力学、递送和毒性相关的障碍，以便将miRNA的潜力转化为有效的抗癌药物。
