Kazemi Masoumeh, Naghdi Sadeh Reza, Shekari Khaniani Mahmoud, Rezazadeh Maryam, Derakhshan Sima Mansoori, Ghafouri-Fard Soudeh
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Sci Rep. 2024 Dec 28;14(1):31192. doi: 10.1038/s41598-024-82490-9.
Alzheimer's disease (AD) is a degenerative illness that accounts for the common type of dementia among adults over the age of 65. Despite extensive studies on the pathogenesis of the disease, early diagnosis of AD is still debatable. In this research, we performed bioinformatics approaches on the AD-related E-MTAB 6094 dataset to uncover new potential biomarkers for AD diagnosis. To achieve this, we performed in-depth in silico assays, including differentially expressed genes analysis, weighted gene co-expression network analyses, module-trait association analyses, gene ontology and pathway enrichment analyses, and hub genes network analyses. Finally, the expression of the identified candidate genes was evaluated in AD patients PBMC samples by qRT-PCR. Through computational analyses, we found that RN7SK LncRNA and its co-expressed genes of TNF, TNFAIP3, CCLT3, and FLT3 are from key genes in AD development that are associated with inflammatory responses. Our experimental validation revealed that RN7SK LncRNA and TNF were substantially up-regulated in AD samples (P = 0.006 and P = 0.023, respectively). Whereas, TNFAIP3 expression was significantly decreased (P = 0.016). However, the expression of CCL3 and FLT3 did not differ significantly between two groups (P = 0.396 and P = 0.521, respectively). In conclusion, in this study a novel LncRNA associated with AD pathogenesis were identified, which may provide new diagnostic biomarker for AD.
阿尔茨海默病(AD)是一种退行性疾病,是65岁以上成年人中常见的痴呆类型。尽管对该疾病的发病机制进行了广泛研究,但AD的早期诊断仍存在争议。在本研究中,我们对与AD相关的E-MTAB 6094数据集进行了生物信息学分析,以发现用于AD诊断的新的潜在生物标志物。为实现这一目标,我们进行了深入的计算机分析,包括差异表达基因分析、加权基因共表达网络分析、模块-性状关联分析、基因本体和通路富集分析以及枢纽基因网络分析。最后,通过qRT-PCR在AD患者的外周血单核细胞(PBMC)样本中评估了所鉴定候选基因的表达。通过计算分析,我们发现RN7SK长链非编码RNA(LncRNA)及其共表达的肿瘤坏死因子(TNF)、肿瘤坏死因子α诱导蛋白3(TNFAIP3)、趋化因子CCL3(CCLT3)和FMS样酪氨酸激酶3(FLT3)基因是AD发展中的关键基因,与炎症反应相关。我们的实验验证表明,RN7SK LncRNA和TNF在AD样本中显著上调(分别为P = 0.006和P = 0.023)。而TNFAIP3表达显著降低(P = 0.016)。然而,两组之间CCL3和FLT3的表达没有显著差异(分别为P = 0.396和P = 0.521)。总之,本研究鉴定了一种与AD发病机制相关的新型LncRNA,这可能为AD提供新的诊断生物标志物。