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对miR-34a在视网膜母细胞瘤中治疗潜力的分子洞察。

Molecular insight into the therapeutic potential of miR-34a in retinoblastoma.

作者信息

Goleij Pouya, Tabari Mohammad Amin Khazeei, Rezaee Aryan, Sanaye Pantea Majma, Kheirandish Ali, Alsharif Khalaf F, Daglia Maria, Larsen Danaé S, Khan Haroon, Poudineh Mohadeseh

机构信息

USERN Office, Kermanshah University of Medical Sciences, Kermanshah, 6715847141, Iran.

Department of Genetics, Faculty of Biology, Sana Institute of Higher Education, Sari, 4816118761, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 22. doi: 10.1007/s00210-025-04463-7.

Abstract

Retinoblastoma (RB) is the predominant type of eye cancer in children, particularly affecting those under three. Early diagnosis is crucial as RB can be fatal if left untreated. MicroRNAs (miRNAs), non-coding RNAs, have emerged as significant regulators of various cellular processes and are increasingly recognized for their influence on RB development and treatment resistance. Dysregulation of miR-34a expression has been implicated in various aspects of tumorigenesis, including processes critical for cancer progression: epithelial-mesenchymal transition (EMT) within the tumor, invasive growth, and metastasis. Furthermore, a deeper understanding of the molecular mechanisms underlying miR-34a function in RB is crucial for the development of effective diagnostic tools and therapeutic strategies. The abundance of miR-34a is further fine-tuned through context-dependent feedback loops. This review comprehensively examines the current understanding of miR-34a's functions in various human diseases. We focus on how miR-34a expression is regulated and disrupted, its involvement in human cancers specifically RB, and its potential as a biomarker for disease diagnosis and prognosis. Additionally, we explore the potential of miR-34a as a novel therapeutic target in RB.

摘要

视网膜母细胞瘤(RB)是儿童最主要的眼癌类型,尤其影响三岁以下儿童。早期诊断至关重要,因为RB若不治疗可能会致命。微小RNA(miRNA)作为非编码RNA,已成为各种细胞过程的重要调节因子,并因其对RB发展和治疗耐药性的影响而日益受到认可。miR-34a表达失调与肿瘤发生的各个方面有关,包括对癌症进展至关重要的过程:肿瘤内的上皮-间质转化(EMT)、侵袭性生长和转移。此外,深入了解miR-34a在RB中发挥作用的分子机制对于开发有效的诊断工具和治疗策略至关重要。miR-34a的丰度通过依赖于上下文的反馈回路进一步微调。本综述全面审视了目前对miR-34a在各种人类疾病中功能的理解。我们重点关注miR-34a的表达如何被调节和破坏,它在人类癌症特别是RB中的作用,以及它作为疾病诊断和预后生物标志物的潜力。此外,我们还探讨了miR-34a作为RB新型治疗靶点的潜力。

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