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调控癌症中的微小RNA:新一代疗法。

Modulating microRNAs in cancer: Next-generation therapies.

作者信息

Arghiani Nahid, Shah Khalid

机构信息

Center for Stem Cell and Translational Immunotherapy (CSTI), Harvard Medical School, Boston, MA 02115, USA.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Cancer Biol Med. 2021 Dec 1;19(3):289-304. doi: 10.20892/j.issn.2095-3941.2021.0294.

Abstract

MicroRNAs (miRNAs) are a class of endogenously expressed non-coding regulators of the genome with an ability to mediate a variety of biological and pathological processes. There is growing evidence demonstrating frequent dysregulation of microRNAs in cancer cells, which is associated with tumor initiation, development, migration, invasion, resisting cell death, and drug resistance. Studies have shown that modulation of these small RNAs is a novel and promising therapeutic tool in the treatment of a variety of diseases, especially cancer, due to their broad influence on multiple cellular processes. However, suboptimal delivery of the appropriate miRNA to the cancer sites, quick degradation by nucleases in the blood circulation, and off target effects have limited their research and clinical applications. Therefore, there is a pressing need to improve the therapeutic efficacy of miRNA modulators, while at the same time reducing their toxicities. Several delivery vehicles for miRNA modulators have been shown to be effective and . In this review, we will discuss the role and importance of miRNAs in cancer and provide perspectives on currently available carriers for miRNA modulation. We will also summarize the challenges and prospects for the clinical translation of miRNA-based therapeutic strategies.

摘要

微小RNA(miRNA)是一类内源性表达的基因组非编码调节因子,具有介导多种生物学和病理过程的能力。越来越多的证据表明,癌细胞中微小RNA经常失调,这与肿瘤的发生、发展、迁移、侵袭、抵抗细胞死亡和耐药性有关。研究表明,由于这些小RNA对多种细胞过程具有广泛影响,调节它们是治疗多种疾病,尤其是癌症的一种新颖且有前景的治疗工具。然而,将合适的miRNA欠佳地递送至癌症部位、在血液循环中被核酸酶快速降解以及脱靶效应限制了它们的研究和临床应用。因此,迫切需要提高miRNA调节剂的治疗效果,同时降低其毒性。已证明几种用于miRNA调节剂的递送载体是有效的。在本综述中,我们将讨论miRNA在癌症中的作用和重要性,并对目前可用的用于miRNA调节的载体提供观点。我们还将总结基于miRNA的治疗策略临床转化面临的挑战和前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5b8/8958885/0d1ff498ed9a/cbm-19-289-g001.jpg

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