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微小RNA作为多发性骨髓瘤治疗的潜在靶点——当前认知与展望

MiRNA as a Potential Target for Multiple Myeloma Therapy-Current Knowledge and Perspectives.

作者信息

Szudy-Szczyrek Aneta, Ahern Sean, Krawczyk Janusz, Szczyrek Michał, Hus Marek

机构信息

Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland.

Department of Haematology, University Hospital Galway, H91 Galway, Ireland.

出版信息

J Pers Med. 2022 Aug 31;12(9):1428. doi: 10.3390/jpm12091428.

Abstract

Multiple myeloma (MM) is the second most common hematological malignancy. Despite the huge therapeutic progress thanks to the introduction of novel therapies, MM remains an incurable disease. Extensive research is currently ongoing to find new options. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post-transcriptional level. Aberrant expression of miRNAs in MM is common. Depending on their role in MM development, miRNAs have been reported as oncogenes and tumor suppressors. It was demonstrated that specific miRNA alterations using miRNA mimics or antagomirs can normalize the gene regulatory network and signaling pathways in the microenvironment and MM cells. These properties make miRNAs attractive targets in anti-myeloma therapy. However, only a few miRNA-based drugs have been entered into clinical trials. In this review, we discuss the role of the miRNAs in the pathogenesis of MM, their current status in preclinical/clinical trials, and the mechanisms by which miRNAs can theoretically achieve therapeutic benefit in MM treatment.

摘要

多发性骨髓瘤(MM)是第二常见的血液系统恶性肿瘤。尽管由于引入了新型疗法,治疗取得了巨大进展,但MM仍然是一种无法治愈的疾病。目前正在进行广泛研究以寻找新的治疗选择。微小RNA(miRNA)是小的非编码RNA分子,在转录后水平调节基因表达。MM中miRNA的异常表达很常见。根据它们在MM发生发展中的作用,miRNA被报道为癌基因和肿瘤抑制因子。研究表明,使用miRNA模拟物或拮抗剂进行特定的miRNA改变可以使微环境和MM细胞中的基因调控网络和信号通路正常化。这些特性使miRNA成为抗骨髓瘤治疗中具有吸引力的靶点。然而,只有少数基于miRNA的药物进入了临床试验。在这篇综述中,我们讨论了miRNA在MM发病机制中的作用、它们在临床前/临床试验中的现状,以及miRNA理论上在MM治疗中实现治疗益处的机制。

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