通过研究微RNA与ALDH1A1的生物学联系,发现了可用于急性髓性白血病临床前测试的候选药物。

IF 4.5 3区 医学 Q1 ONCOLOGY International journal of oncology Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI:10.3892/ijo.2024.5703
Spiros A Vlahopoulos, Lokman Varisli, Panagiotis Zoumpourlis, Demetrios A Spandidos, Vassilis Zoumpourlis
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引用次数: 0

摘要

醛脱氢酶 1 家族成员 A1(ALDH1A1)是醛脱氢酶基因亚家族的成员,该亚家族编码的酶具有氧化视黄醛的能力。最近的研究表明,高 ALDH1A1 RNA 丰度与急性髓性白血病(AML)的不良预后相关。急性髓性白血病是一种与高发病率和高死亡率相关的造血恶性肿瘤。虽然有许多药物可以抑制 ALDH 的活性,但关键是要开发出可调整的基因干扰方法,这样才能同时对几种致癌途径进行干预。微小核糖核酸(miRNA 或 miRs)是一类小型非编码 RNA,已成为急性髓细胞性白血病基因表达的关键调控因子,理论上可以对多种致癌途径进行干预。一些 miRNAs 已显示出直接干扰实体肿瘤细胞中 ALDH1A1 基因表达的能力,这些 miRNAs 可在急性髓细胞性白血病模型系统中进行评估。有迹象表明,其中一些 miRNA 确实与急性髓细胞性白血病的病程有关,因此有希望成为对急性髓细胞性白血病细胞进行基因干预的靶点。
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Investigating the biology of microRNA links to ALDH1A1 reveals candidates for preclinical testing in acute myeloid leukemia.

Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is a member of the aldehyde dehydrogenase gene subfamily that encode enzymes with the ability to oxidize retinaldehyde. It was recently shown that high ALDH1A1 RNA abundance correlates with a poor prognosis in acute myeloid leukemia (AML). AML is a hematopoietic malignancy associated with high morbidity and mortality rates. Although there are a number of agents that inhibit ALDH activity, it would be crucial to develop methodologies for adjustable genetic interference, which would permit interventions on several oncogenic pathways in parallel. Intervention in multiple oncogenic pathways is theoretically possible with microRNAs (miRNAs or miRs), a class of small non‑coding RNAs that have emerged as key regulators of gene expression in AML. A number of miRNAs have shown the ability to interfere with ALDH1A1 gene expression directly in solid tumor cells, and these miRNAs can be evaluated in AML model systems. There are indications that a few of these miRNAs actually do have an association with AML disease course, rendering them a promising target for genetic intervention in AML cells.

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157
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2.1 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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