Voropaeva Elena N, Orlov Yuriy L, Loginova Anastasia B, Seregina Olga B, Maksimov Vladimir N, Pospelova Tatiana I
Research Institute of Internal and Preventive Medicine - Branch of the Federal State Budget Scientific Institution "The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences", Novosibirsk, Russia.
Novosibirsk State Medical University of the Ministry of Health of the Russian Federation, Novosibirsk, Russia.
PeerJ. 2025 Jan 7;13:e18661. doi: 10.7717/peerj.18661. eCollection 2025.
Here, we have discussed the molecular mechanisms of p53-responsive microRNAs dysregulation in response to genotoxic stress in diffuse large B-cell lymphoma (DLBCL) patients. The role of micro ribonucleic acids (microRNAs) in p53-signaling cellular stress has been studied. MicroRNAs are the small non-coding RNAs, which regulate genes expression at post-transcriptional level. Many of them play a crucial role in carcinogenesis and may act as oncogenes or suppressor of tumor growth. The understanding of the effect of p53-responsive microRNA dysregulation on oncogenesis achieved in recent decades opens wide opportunities for the diagnosis, prediction and of microRNA-based cancer therapy. Development of new bioinformatics tools and databases for microRNA supports DLBCL research. We overview the studies on the role of miRNAs in regulating gene expression associated with tumorigenesis processes, with particular emphasis on their role as tumor growth-suppressing factors. The starting point is a brief description of the classical microRNA biogenesis pathway and the role of p53 in regulating the expression of these molecules. We analyze various molecular mechanisms leading to this dysregulation, including mutations in the gene, DNA methylation, changes in host-genes expression or microRNA gene copy number, mutations in microRNA and microRNA biogenesis genes.
在此，我们讨论了弥漫性大B细胞淋巴瘤（DLBCL）患者中p53反应性微小RNA失调在应对基因毒性应激时的分子机制。微小核糖核酸（微小RNA）在p53信号传导细胞应激中的作用已得到研究。微小RNA是小的非编码RNA，其在转录后水平调节基因表达。它们中的许多在致癌过程中起关键作用，并且可能充当癌基因或肿瘤生长抑制因子。近几十年来对p53反应性微小RNA失调对肿瘤发生的影响的认识为基于微小RNA的癌症诊断、预测和治疗开辟了广阔的机会。用于微小RNA的新生物信息学工具和数据库的开发支持了DLBCL研究。我们概述了关于微小RNA在调节与肿瘤发生过程相关的基因表达中的作用的研究，特别强调了它们作为肿瘤生长抑制因子的作用。起点是对经典微小RNA生物发生途径以及p53在调节这些分子表达中的作用的简要描述。我们分析了导致这种失调的各种分子机制，包括基因中的突变、DNA甲基化、宿主基因表达或微小RNA基因拷贝数的变化、微小RNA和微小RNA生物发生基因中的突变。
