Profiling non-coding RNA expression in cerebrospinal fluid of amyotrophic lateral sclerosis patients.
Profiling non-coding RNA expression in cerebrospinal fluid of amyotrophic lateral sclerosis patients.
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DOI：
10.1080/07853890.2022.2138530
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发表时间：
2022-12
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
致死性神经退行性疾病肌萎缩性侧索硬化症或运动神经元疾病（ALS/MND）的生物标志物对于诊断、药物开发、临床试验和了解疾病病理至关重要。生物液体中存在的生物标志物的主要候选物包括非编码RNA （ncRNA）转录物，包括microRNA、piwi相互作用RNA和转移RNA。为了确定中枢神经系统是否是我们之前在血清中观察到的失调的ncRNA生物标志物的来源，我们试图在脑脊液（CSF）中识别失调的ncRNA候选物，这可能为疾病病理学提供新的见解。我们对来自健康对照（n = 18）、疾病模拟（n = 8）和ALS患者（n = 40）的CSF样本进行了小RNA测序（RNA-seq），并使用RT-qPCR确认其失调。我们在RNA-seq筛选中发现了一系列失调的ncRNA，但在某些情况下，使用逆转录定量聚合酶链反应（RT-qPCR）无法验证或检测到这些ncRNA。此外，我们之前鉴定的血清ncRNA生物标志物显示CSF没有变化或与血清相关。在本研究中，我们研究了ALS患者脑脊液中非编码RNA转录物的表达与健康对照组的比较。RNA-seq鉴定出了失调的非编码RNA转录物，但这些转录物并没有通过RT-qPCR验证。我们得出结论，脑脊液不是诊断性生物标志物的合适来源。该研究提示CSF可能不是血清中失调ncRNA的来源，并强调了鉴定CSF中ncRNA作为ALS生物标志物的难度。
Objective biomarkers for the fatal neurodegenerative disease amyotrophic lateral sclerosis or motor neuron disease (ALS/MND) are critical for diagnosis, drug development, clinical trials, and insight into disease pathology. Key candidates for biomarkers present in biofluids include non-coding RNA (ncRNA) transcripts including microRNA, piwi-interacting RNA and transfer RNA. To determine if the central nervous system was the source of the dysregulated ncRNA biomarkers we previously observed in serum, we sought to identify dysregulated ncRNA candidates in cerebrospinal fluid (CSF) which may provide new insight into the disease pathology. Small RNA sequencing (RNA-seq) was undertaken on CSF samples from healthy controls (n = 18), disease mimics (n = 8), and ALS patients (n = 40) in our Oxford Study for Biomarkers of ALS cohort, with RT-qPCR used to confirm their dysregulation. We found a range of ncRNA that were dysregulated in the RNA-seq screen, but these failed to be validated or detected in some cases using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, our previously identified serum ncRNA biomarker showed no change in CSF or correlation to serum. In this current study, we investigated the expression of non-coding RNA transcripts in the cerebrospinal fluid of ALS patients compared to healthy controls. RNA-seq identified dysregulated non-coding RNA transcripts, but these were not validated with RT-qPCR. We conclude that cerebrospinal fluid is not a suitable source of diagnostic biomarkers. This study suggests the CSF may not be the source of dysregulated ncRNA in the serum and highlights the difficulty in identifying ncRNA in CSF as biomarkers for ALS.
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感染诱导的Trnahisgug的5 half分子激活类似收费的受体7。
影响因子：
9.8
作者：
Pawar K;Shigematsu M;Sharbati S;Kirino Y
通讯作者：
Kirino Y
影响因子：
2.7
作者：
Fernández-Messina L;Gutiérrez-Vázquez C;Rivas-García E;Sánchez-Madrid F;de la Fuente H
通讯作者：
de la Fuente H
DOI：
10.1126/science.1181046
发表时间：
2009-12-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Williams AH;Valdez G;Moresi V;Qi X;McAnally J;Elliott JL;Bassel-Duby R;Sanes JR;Olson EN
通讯作者：
Olson EN
影响因子：
4.7
作者：
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通讯作者：
Hashido, Kazuo
影响因子：
4.4
作者：
de Andrade, Helen M. T.;de Albuquerque, Milena;Franca, Marcondes C., Jr.
通讯作者：
Franca, Marcondes C., Jr.