Department of Biomedical and Biotechnological Sciences, University of Catania, I‑95123 Catania, Italy.
Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece.
Oncol Rep. 2019 Sep;42(3):911-922. doi: 10.3892/or.2019.7215. Epub 2019 Jun 28.
There is recent evidence to indicate the existence of an inverse association between the incidence of neurological disorders and cancer development. Concurrently, the transcriptional pathways responsible for the onset of glioblastoma multiforme (GBM) and Alzheimer's disease (AD) have been found to be mutually exclusive between the two pathologies. Despite advancements being made concerning the knowledge of the molecular mechanisms responsible for the development of GBM and AD, little is known about the identity of the microRNA (miRNAs or miRs) involved in the development and progression of these two pathologies and their possible inverse expression patterns. On these bases, the aim of the present study was to identify a set of miRNAs significantly de‑regulated in both GBM and AD, and hence to determine whether the identified miRNAs exhibit an inverse association within the two pathologies. For this purpose, miRNA expression profiling datasets derived from the Gene Expression Omnibus (GEO) DataSets and relative to GBM and AD were used. Once the miRNAs significantly de‑regulated in both pathologies were identified, DIANA‑mirPath pathway prediction and STRING Gene Ontology enrichment analyses were performed to establish their functional roles in each of the pathologies. The results allowed the identification of a set of miRNAs found de‑regulated in both GBM and AD, whose expression levels were inversely associated in the two pathologies. In particular, a strong negative association was observed between the expression levels of miRNAs in GBM compared to AD, suggesting that although the molecular pathways behind the development of these two pathologies are the same, they appear to be inversely regulated by miRNAs. Despite the identification of this set of miRNAs which may be used for diagnostic, prognostic and therapeutic purposes, further functional in vitro and in vivo evaluations are warranted in order to validate the diagnostic and therapeutic potential of the identified miRNAs, as well as their involvement in the development of GBM and AD.
最近有证据表明,神经紊乱疾病的发病率与癌症的发展之间存在反比关系。同时,人们发现胶质母细胞瘤多形性(GBM)和阿尔茨海默病(AD)发病的转录途径在这两种病理之间是相互排斥的。尽管人们在了解导致 GBM 和 AD 发展的分子机制方面取得了进展,但对于参与这两种疾病发展和进展的 microRNA(miRNAs 或 miRs)的身份以及它们可能的反式表达模式知之甚少。基于这些原因,本研究旨在鉴定一组在 GBM 和 AD 中均显著下调的 miRNAs,并确定鉴定出的 miRNAs 在这两种疾病中是否存在反比关系。为此,使用了来自基因表达综合数据库(GEO)数据集的与 GBM 和 AD 相关的 miRNA 表达谱数据集。一旦确定了在两种疾病中均显著下调的 miRNAs,就进行 DIANA-mirPath 途径预测和 STRING 基因本体论富集分析,以确定它们在每种疾病中的功能作用。结果鉴定出一组在 GBM 和 AD 中均下调的 miRNAs,它们在两种疾病中的表达水平呈反比关系。特别是,与 AD 相比,GBM 中 miRNA 的表达水平存在强烈的负相关,这表明尽管这两种疾病发展背后的分子途径相同,但它们似乎被 miRNAs 反向调节。尽管鉴定出了这组可能用于诊断、预后和治疗目的的 miRNAs,但仍需要进一步进行体外和体内功能评估,以验证鉴定出的 miRNAs 的诊断和治疗潜力,以及它们在 GBM 和 AD 发展中的参与情况。