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miRNA-34 家族:癌症中一种潜在的肿瘤抑制因子和治疗靶点。

MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer.

机构信息

Key Laboratory of Biorheological Science and Technology, Ministlry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.

Department of thoracic surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

出版信息

J Exp Clin Cancer Res. 2019 Feb 4;38(1):53. doi: 10.1186/s13046-019-1059-5.

Abstract

MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized. miR-34 plays a crucial role on repressing tumor progression by involving in epithelial-mesenchymal transition (EMT) via EMT- transcription factors, p53 and some important signal pathways. Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems. Here, we provide an overview about the function of miR-34 in various cancers and the mechanism of miR-34 in tumor-associated EMT. Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected.

摘要

微 RNA-34(miR-34)在各种人类癌症中失调已被报道,并因其与著名的肿瘤抑制因子 p53 的协同作用而被视为肿瘤抑制 microRNA。随着基于 miR-34a 模拟物的首个肿瘤靶向 microRNA 药物 MRX34 的应用,在 I 期临床试验(NCT01829971)中,miR-34 的意义日益得到认可。miR-34 通过 EMT-转录因子、p53 和一些重要信号通路参与上皮-间充质转化(EMT),在抑制肿瘤进展中发挥着关键作用。不仅如此,大量的临床前研究通过多种纳米级递药系统揭示了 miR-34a 在癌症治疗中的巨大潜力。在这里,我们综述了 miR-34 在各种癌症中的功能及其在肿瘤相关 EMT 中的作用机制。此外,还讨论了它作为 microRNA 治疗候选物的潜在作用。尽管存在一些障碍,但 miR-34 在肿瘤治疗中的广泛应用前景不容忽视。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44c2/6360685/1222c2c17fbf/13046_2019_1059_Fig1_HTML.jpg

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