共济失调毛细血管扩张症 (AT) 是一种罕见疾病，其特征是神经变性、联合免疫缺陷、恶性肿瘤倾向和高度临床变异。 microRNA (miRNA) 的分析可能有助于深入了解复杂的罕见人类疾病的潜在机制，因为 miRNA 在增殖、分化和 DNA 修复等多种生物学功能中发挥着重要作用。在这项研究中，我们研究了 AT 患者样本中 miRNA 的差异表达，以识别 miRNA 模式并分析这些模式与疾病的关系。我们招募了 20 名 AT 患者（平均年龄 17.7 ± 9.6 岁）并收集了临床和遗传信息。数据。我们对外周血单核细胞 (PBMC) 和成纤维细胞进行了简短的非编码 RNA 测序分析，以比较 AT 患者和对照之间的 miRNA 表达谱。我们在血液样本中观察到 42 个差异表达 (DE)-miRNA，在成纤维细胞样本中观察到 26 个差异表达 (DE)-miRNA 。其中，三种 DE-miRNA，miR-342-3p、miR-30a-5p 和 miR-195-5p，在其他 AT 样本中得到了进一步验证，证实了它们的失调。我们在血细胞中鉴定了与 AT 相关的 miRNA 特征和从一组 AT 患者收集的成纤维细胞样本。我们还预测了一些失调的途径，主要与癌症、免疫系统控制或炎症过程有关。研究结果表明，miRNA 可以深入了解 AT 的病理生理学和肿瘤发生，并有可能在癌症研究中作为有用的生物标志物。版权所有 © 2024 Cirillo, Tarallo, Toriello, Carissimo, Giardino, De Rosa, Damiano, Soresina, Badolato, Dellepiane、巴塞利、卡拉巴、法比奥、贝尔托里尼、蒙坦、孔蒂、罗马诺、波齐、费雷罗、龙卡拉蒂、费拉辛、布鲁斯科、帕伦蒂和皮尼亚塔。

Ataxia telangiectasia (AT) is a rare disorder characterized by neurodegeneration, combined immunodeficiency, a predisposition to malignancies, and high clinical variability. Profiling of microRNAs (miRNAs) may offer insights into the underlying mechanisms of complex rare human diseases, as miRNAs play a role in various biological functions including proliferation, differentiation, and DNA repair. In this study, we investigate the differential expression of miRNAs in samples from AT patients to identify miRNA patterns and analyze how these patterns are related to the disease.We enrolled 20 AT patients (mean age 17.7 ± 9.6 years old) and collected clinical and genetic data. We performed short non-coding RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and fibroblasts to compare the miRNA expression profile between AT patients and controls.We observed 42 differentially expressed (DE)-miRNAs in blood samples and 26 in fibroblast samples. Among these, three DE-miRNAs, miR-342-3p, miR-30a-5p, and miR-195-5p, were further validated in additional AT samples, confirming their dysregulation.We identified an AT-related miRNA signature in blood cells and fibroblast samples collected from a group of AT patients. We also predicted several dysregulated pathways, primarily related to cancer, immune system control, or inflammatory processes. The findings suggest that miRNAs may provide insights into the pathophysiology and tumorigenesis of AT and have the potential to serve as useful biomarkers in cancer research.Copyright © 2024 Cirillo, Tarallo, Toriello, Carissimo, Giardino, De Rosa, Damiano, Soresina, Badolato, Dellepiane, Baselli, Carrabba, Fabio, Bertolini, Montin, Conti, Romano, Pozzi, Ferrero, Roncarati, Ferracin, Brusco, Parenti and Pignata.