Amirkhah R, Farazmand A, Irfan-Maqsood M, Wolkenhauer O, Schmitz U
University of Tehran Department of Cell and Molecular Biology, School of Biology, College of Science Tehran Iran.
University of Tehran Department of Cell and Molecular Biology, School of Biology, College of Science Tehran Iran afarazmand@khayam.ut.ac.ir.
Cell Mol Biol (Noisy-le-grand). 2015 Oct 30;61(6):17-23.
Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Several approaches such as surgery, chemotherapy, radiotherapy, targeted therapy, or combinations thereof have been used to treat CRC patients. However, the fact that many patients develop a drug resistance during the course of the treatment is a major obstacle. Understanding the mechanisms underlying resistance is critical in order to develop more effective targeted treatments. Recently, several studies have reported on the regulatory role of microRNAs (miRNAs) in the response to anti-cancer drugs and suggested them as a source of predictive biomarkers for the purpose of patient stratification and for the prognosis of treatment success. For example, overexpressing miR-34a, a master regulator of tumor suppression attenuates chemoresistance to 5-FU by downregulating silent information regulator 1 (SIRT1) and E2F3. MRX34, a miR-34a replacement is the first synthetic miRNA mimic to enter clinical testing. MiR-34a antagonizes cancer stemness, metastasis, and chemoresistance processes that are necessary for cancer viability. This example shows that miRNAs are coming into focus for the design of enhanced cancer therapies that aim to sensitise tumor cells for anti-cancer drugs. In this review, we provide an overview on the role of miRNAs in the resistance to current colorectal cancer therapies. Furthermore, we discuss the value of miRNAs as biomarkers for predicting chemosensitivity and their potential to enhance treatment strategies.
结直肠癌（CRC）是全球癌症相关死亡的主要原因之一。手术、化疗、放疗、靶向治疗或其联合使用等多种方法已被用于治疗CRC患者。然而，许多患者在治疗过程中产生耐药性这一事实是一个主要障碍。了解耐药的潜在机制对于开发更有效的靶向治疗至关重要。最近，几项研究报道了微小RNA（miRNA）在抗癌药物反应中的调节作用，并建议将它们作为预测生物标志物的来源，用于患者分层和治疗成功的预后评估。例如，过表达miR-34a（一种肿瘤抑制的主要调节因子）通过下调沉默信息调节因子1（SIRT1）和E2F3来减弱对5-氟尿嘧啶的化疗耐药性。MRX34，一种miR-34a替代物，是第一个进入临床试验的合成miRNA模拟物。miR-34a拮抗癌症干性、转移和化疗耐药过程，这些过程是癌症存活所必需的。这个例子表明，miRNA正成为旨在使肿瘤细胞对抗癌药物敏感的增强癌症治疗设计的焦点。在这篇综述中，我们概述了miRNA在当前结直肠癌治疗耐药中的作用。此外，我们讨论了miRNA作为预测化疗敏感性的生物标志物的价值及其增强治疗策略的潜力。
