Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis

Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis
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DOI:
10.1007/s12035-019-1627-x
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发表时间:
2019-12-01
影响因子:
5.1
通讯作者:
Ravnik-Glavac, Metka
Ravnik-Glavac, Metka
中科院分区:
医学2区
文献类型:
--
作者:
Dolinar, Ana;Koritnik, Blaz;Ravnik-Glavac, Metka

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环状rna (circRNAs)在许多人类疾病中作为一种新颖而强大的角色出现。它们参与了几个细胞过程,并正在成为一种值得注意的生物标志物。在其他功能中,环状RNA可以作为RNA海绵或RNA结合蛋白的支架。在这里,我们研究了来自ALS患者和年龄和性别匹配的健康对照的白细胞样本中环状rna的微阵列表达谱,以鉴定差异表达的环状rna。我们选择了其中的10个进行qPCR验证,在更大的样本集上表达,鉴定它们与临床参数的关联,并评估它们的诊断潜力。总的来说,与年龄和性别匹配的健康对照组相比,在更大的ALS患者队列中,7/10 circrna的表达是显著的。其中三个(hsa_circ_0023919, hsa_circ_0063411和hsa_circ_0088036)显示出与微阵列结果相同的调节。这三种环状rna的AUC均为>.95,对最佳阈值的敏感性和特异性均为> 90%,显示出它们作为诊断性生物标志物的潜力。
Circular RNAs (circRNAs) are emerging as a novel, yet powerful player in many human diseases. They are involved in several cellular processes and are becoming a noteworthy type of biomarkers. Among other functions, circRNAs can serve as RNA sponges or as scaffolds for RNA-binding proteins. Here, we investigated a microarray expression profile of circRNAs in leukocyte samples from ALS patients and age- and sex-matched healthy controls to identify differentially expressed circRNAs. We selected 10 of them for a qPCR validation of expression on a larger set of samples, identification of their associations with clinical parameters, and evaluation of their diagnostic potential. In total, expression of 7/10 circRNAs was significant in a larger cohort of ALS patients, compared with age- and sex-matched healthy controls. Three of them (hsa_circ_0023919, hsa_circ_0063411, and hsa_circ_0088036) showed the same regulation as in microarray results. These three circRNAs also had AUC > 0.95, and sensitivity and specificity for the optimal threshold point > 90%, showing their potential for using them as diagnostic biomarkers.