循环lncRNA HOTAIR是儿童急性淋巴细胞白血病的生物标志物和miR-326外泌体输出的中介。

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Neda Rahimi Dashti, Dorsa Fadavi, Razieh Rezaei, Soheila Rahgozar, Alireza Moafi
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引用次数: 0

摘要

急性淋巴细胞白血病(ALL)是全世界儿童中最常见的癌症。在本研究中,循环rna (circRNAs) HOTAIR、NEAT1、H19、PCAT1和SNHG1被选择作为儿童ALL (pALL)的潜在生物标志物,基于它们与miR-326(一种与pALL有关的公认的肿瘤抑制因子)的预测相互作用,以及全面的计算机分析。随后,使用RT-qPCR检测了50个pALL样本和20个健康对照中circrna的表达水平。值得注意的是,HOTAIR被确定为95%的癌症易感性特异性生物标志物,在骨髓血浆和外周血样本中的表达显著增加。22例circHOTAIR相对表达水平升高(≥1.87)的B-ALL患者在化疗期间的三个不同时间间隔进行监测。结果显示,HOTAIR表达仅在治疗敏感的患者中显著降低(P
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Circulating lncRNA HOTAIR is a biomarker for pediatric acute lymphoblastic leukemia and mediator of miR-326 exosomal export.

Circulating lncRNA HOTAIR is a biomarker for pediatric acute lymphoblastic leukemia and mediator of miR-326 exosomal export.

Circulating lncRNA HOTAIR is a biomarker for pediatric acute lymphoblastic leukemia and mediator of miR-326 exosomal export.

Circulating lncRNA HOTAIR is a biomarker for pediatric acute lymphoblastic leukemia and mediator of miR-326 exosomal export.

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children worldwide. In the present investigation, the circulating RNAs (circRNAs) HOTAIR, NEAT1, H19, PCAT1, and SNHG1 were selected as potential biomarkers for childhood ALL (pALL) based on their predicted interactions with miR-326, a recognized tumor suppressor implicated in pALL, along with comprehensive in silico analyses. Subsequently, the expression levels of the circRNAs were examined in 50 pALL samples and 20 healthy controls using RT-qPCR. Notably, HOTAIR was identified as a 95% specific biomarker of cancer susceptibility, exhibiting a substantial increase in expression within the bone marrow plasma and peripheral blood samples. 22 B-ALL patients with elevated relative expression levels of circHOTAIR (≥ 1.87) were then monitored at three distinct time intervals during chemotherapy. Results demonstrated a significant decrease in HOTAIR expression only among treatment-sensitive patients (P < 0.0001). This finding positions HOTAIR as a novel prognostic factor (AUC = 0.955), which may be used for monitoring the efficacy of chemotherapy in a non-invasive, cost-effective manner. Additionally, the regulatory inter-connection between HOTAIR and miR-326 was investigated by transfecting B-ALL RN-95 cells with exogenous miR-326. Data showed a time-dependent increase in cytoplasmic HOTAIR levels, alongside RAB35, resulting in a corresponding reduction in the cytoplasmic and exosomal miR-326 levels. While the results are preliminary due to the sample size, this study is the first to identify circHOTAIR as both a prognostic and diagnostic biomarker in B-ALL. Furthermore, it elucidates the role of HOTAIR as a sponge for miR-326, orchestrating its efflux from the cell via exosomes through RAB35.

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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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