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微小 RNA:癌症治疗中的大有可为的角色。

MicroRNA: Promising Roles in Cancer Therapy.

机构信息

Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Curr Pharm Biotechnol. 2020;21(12):1186-1203. doi: 10.2174/1389201021666200420101613.

Abstract

MicroRNAs (miRNA) are small non-coding RNAs that act as one of the main regulators of gene expression. They are involved in maintaining a proper balance of diverse processes, including differentiation, proliferation, and cell death in normal cells. Cancer biology can also be affected by these molecules by modulating the expression of oncogenes or tumor suppressor genes. Thus, miRNA based anticancer therapy is currently being developed either alone or in combination with chemotherapy agents used in cancer management, aiming at promoting tumor regression and increasing cure rate. Access to large quantities of RNA agents can facilitate RNA research and development. In addition to currently used in vitro methods, fermentation-based approaches have recently been developed, which can cost-effectively produce biological RNA agents with proper folding needed for the development of RNA-based therapeutics. Nevertheless, a major challenge in translating preclinical studies to clinical for miRNA-based cancer therapy is the efficient delivery of these agents to target cells. Targeting miRNAs/anti-miRNAs using antibodies and/or peptides can minimize cellular and systemic toxicity. Here, we provide a brief review of miRNA in the following aspects: biogenesis and mechanism of action of miRNAs, the role of miRNAs in cancer as tumor suppressors or oncogenes, the potential of using miRNAs as novel and promising therapeutics, miRNA-mediated chemo-sensitization, and currently utilized methods for the in vitro and in vivo production of RNA agents. Finally, an update on the viral and non-viral delivery systems is addressed.

摘要

微小 RNA(miRNA)是一种小的非编码 RNA,作为基因表达的主要调控因子之一。它们参与维持正常细胞中各种过程的适当平衡,包括分化、增殖和细胞死亡。这些分子还可以通过调节癌基因或肿瘤抑制基因的表达来影响癌症生物学。因此,目前正在单独或与癌症管理中使用的化疗药物联合开发基于 miRNA 的抗癌疗法,旨在促进肿瘤消退并提高治愈率。大量 RNA 药物的获得可以促进 RNA 的研究和开发。除了目前使用的体外方法外,最近还开发了基于发酵的方法,可以经济有效地生产具有适当折叠的生物 RNA 药物,这对于开发基于 RNA 的治疗方法是必要的。然而,将 miRNA 为基础的癌症治疗的临床前研究转化为临床实践的主要挑战是这些药物有效递送到靶细胞。使用抗体和/或肽靶向 miRNA/anti-miRNA 可以最小化细胞和全身毒性。在这里,我们简要综述了 miRNA 在以下几个方面的研究进展:miRNA 的生物发生和作用机制、miRNA 在癌症中的作为肿瘤抑制因子或癌基因的作用、将 miRNA 用作新型有前途的治疗剂的潜力、miRNA 介导的化疗增敏作用,以及目前用于 RNA 药物体外和体内生产的方法。最后,介绍了病毒和非病毒递送系统的最新进展。

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