The role of microRNAs in understanding sex-based differences in Alzheimer's disease.

IF 4.9 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Biology of Sex Differences Pub Date : 2024-01-31 DOI:10.1186/s13293-024-00588-1

Jaime Llera-Oyola, Héctor Carceller, Zoraida Andreu, Marta R Hidalgo, Irene Soler-Sáez, Fernando Gordillo, Borja Gómez-Cabañes, Beatriz Roson, Maria de la Iglesia-Vayá, Roberta Mancuso, Franca R Guerini, Akiko Mizokami, Francisco García-García

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引用次数: 0

Abstract

Background: The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment.

Methods: A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms.

Results: Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process.

Conclusions: Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.

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微RNA在理解阿尔茨海默病性别差异中的作用。

背景：阿尔茨海默病（AD）是导致痴呆症的最常见原因，随着全球人口寿命的延长，预计其发病率还会上升。虽然以前曾描述过阿尔茨海默病的性别差异，但性别与疾病相关分子机制之间的关系仍不确定。研究微小RNA（miRNA）等调控因子的性别特异性表达谱有助于更准确地诊断和治疗疾病：方法：通过系统性回顾，在基因表达总库（Gene Expression Omnibus）中找到了六项关于AD患者microRNA表达的研究，这些研究都包含了样本的生物学性别信息。在考虑疾病状态和患者性别的基础上，进行了微RNA表达差异分析。随后，在荟萃分析方法中整合了分析结果，并对荟萃分析结果进行了功能富集，确定了miRNA表达改变与相关基因本体术语之间的关联：血液样本中 miRNA 表达谱的元分析显示，女性 AD 患者和男性 AD 患者分别有 16 个和 22 个 miRNA 发生变化。我们发现有九种miRNA在男女患者中普遍表达过高，这表明男女患者存在共同的miRNA失调特征。基于miRNA图谱的功能富集结果显示了生物过程中的性别差异；男性受影响最大的过程与泛素化、不同激酶活性的调节和细胞凋亡过程有关，而女性则与RNA剪接和翻译有关。对大脑样本中 miRNA 表达谱的元分析表明，女性和男性 AD 患者分别有六种和四种 miRNA 发生了改变。我们在女性和男性AD患者中观察到了一种表达不足的miRNA（hsa-miR-767-5p）；然而，脑样本的功能富集分析并未发现任何具体受影响的生物过程：结论：性别特异性荟萃分析支持在女性和男性AD患者中检测到不同表达的miRNA，突出了生物医学数据中基于性别的信息的相关性。有关AD患者miRNA调控的进一步研究应符合信息的可比性和标准化标准。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY

CiteScore

12.10

自引率

1.30%

发文量

审稿时长

14 weeks

期刊介绍： Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.