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非编码RNA的失调:微小RNA和长链非编码RNA在多发性骨髓瘤发病机制中的作用

Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma.

作者信息

Ismail Nor Hayati, Mussa Ali, Al-Khreisat Mutaz Jamal, Mohamed Yusoff Shafini, Husin Azlan, Al-Jamal Hamid Ali Nagi, Johan Muhammad Farid, Islam Md Asiful

机构信息

Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.

Department of Biology, Faculty of Education, Omdurman Islamic University, Omdurman 11111, Sudan.

出版信息

Noncoding RNA. 2023 Nov 3;9(6):68. doi: 10.3390/ncrna9060068.

Abstract

The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs can serve as oncogenes or tumor suppressors depending on the target genes. In MM, miRNA disruption could result in abnormal gene expression responsible for cell growth, apoptosis, and other biological processes pertinent to cancer development. The dysregulated miRNAs inhibit the activity of tumor suppressor genes, contributing to disease progression. Nonetheless, several miRNAs are downregulated in MM and have been identified as gene regulators implicated in extracellular matrix remodeling and cell adhesion. miRNA depletion potentially facilitates the tumor advancement and resistance of therapeutic drugs. Additionally, lncRNAs are key regulators of numerous cellular processes, such as gene expression, chromatin remodeling, protein trafficking, and recently linked MM development. The lncRNAs are uniquely expressed and influence gene expression that supports MM growth, in addition to facilitating cellular proliferation and viability via multiple molecular pathways. miRNA and lncRNA alterations potentially result in anomalous gene expression and interfere with the regular functioning of MM. Thus, this review aims to highlight the dysregulation of these ncRNAs, which engender novel therapeutic modalities for the treatment of MM.

摘要

非编码RNA(ncRNAs)的失调,特别是微小RNA(miRNAs)和长链非编码RNA(lncRNAs),会导致多发性骨髓瘤(MM)的发生和发展。尤其是miRNAs在转录后基因调控中至关重要,可促进mRNA降解和翻译抑制。因此,根据靶基因的不同,miRNAs可作为癌基因或肿瘤抑制因子。在MM中,miRNA的破坏可能导致负责细胞生长、凋亡及其他与癌症发展相关生物学过程的基因表达异常。失调的miRNAs会抑制肿瘤抑制基因的活性,促进疾病进展。尽管如此,一些miRNAs在MM中表达下调,并已被确定为参与细胞外基质重塑和细胞黏附的基因调节因子。miRNA的缺失可能会促进肿瘤进展和对治疗药物的耐药性。此外,lncRNAs是众多细胞过程的关键调节因子,如基因表达、染色质重塑、蛋白质运输,并且最近与MM的发展相关。lncRNAs独特表达并影响支持MM生长的基因表达,此外还通过多种分子途径促进细胞增殖和存活。miRNA和lncRNA的改变可能导致异常的基因表达,并干扰MM的正常功能。因此,本综述旨在强调这些ncRNAs的失调情况,它们为MM的治疗带来了新的治疗方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55ed/10660696/7925002d3f4b/ncrna-09-00068-g001.jpg

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