Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease

Yin, Xi; Wang, Miao; Wang, Wei; Chen, Tong; Song, Ge; Niu, Yixuan; Jiang, Ziying; Gao, Zhongbao; Wang, Zhenfu

doi:10.1155/2022/2877728

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…MiRNAs can cross the blood-brain barrier and enter body fluids as blood, urine and saliva. In addition, miRNAs are stable, easily quantifiable and accessible by minimally-invasive procedures [6] Several studies have shown that specific panels of miRNAs are dysregulated in PD and other parkinsonian disorders [7,8]. Such evidence shows that the use of miRNAs as biomarkers has great potential for early PD diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Gender differences in microRNA expression in levodopa-naive PD patients

et al. 2023

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Gender is an important factor influencing epidemiological and clinical features of Parkinson’s disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs (miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman’s correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62; p < 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44; p < 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment.

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Section: Introductionmentioning

confidence: 99%

Gender differences in microRNA expression in levodopa-naive PD patients

et al. 2023

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“…In particular, miR-30b-5p levels in serum exosomes helped to distinguish relapsing-remitting from progressive MS ( 43 ). Finally, the levels of miR-30e-5p were downregulated in the blood of patients with Parkinson disease compared with controls ( 44 ), but no reports on the role of miR-30e-5p have been found in MS.…”

Section: Discussionmentioning

confidence: 99%

Molecular signature associated with cladribine treatment in patients with multiple sclerosis

et al. 2023

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IntroductionLittle is known about the molecular profiling associated with the effect of cladribine in patients with multiple sclerosis (MS). Here, we aimed first to characterize the transcriptomic and proteomic profiles induced by cladribine in blood cells, and second to identify potential treatment response biomarkers to cladribine in patients with MS.MethodsGene, protein and microRNA (miRNA) expression profiles were determined by microarrays (genes, miRNAs) and mass spectrometry (proteins) in peripheral blood mononuclear cells (PBMCs) from MS patients after in vitro treatment with cladribine in its active and inactive forms. Two bioinformatics approaches to integrate the three obtained datasets were applied: (i) a multiomics discriminant analysis (DIABLO - Data Integration Analysis for Biomarker discovery using Latent variable approaches for Omics studies); and (ii) a multi-stage integration of features selected in differential expression analysis on each dataset and then merged. Selected molecules from the in vitro study were quantified by qPCR ex vivo in PBMCs from MS patients receiving cladribine.ResultsPBMCs treated in vitro with cladribine were characterized by a major downregulation of gene, protein, and miRNA expression compared with the untreated cells. An intermediate pattern between the cladribine-treated and untreated conditions was observed in PBMCs treated with cladribine in its inactive form. The differential expression analysis of each dataset led to the identification of four genes and their encoded proteins, and twenty-two miRNAs regulating their expression, that were associated with cladribine treatment. Two of these genes (PPIF and NHLRC2), and three miRNAs (miR-21-5p, miR-30b-5p, and miR-30e-5p) were validated ex vivo in MS patients treated with cladribine.DiscussionBy using a combination of omics data and bioinformatics approaches we were able to identify a multiomics molecular profile induced by cladribine in vitro in PBMCs. We also identified a number of biomarkers that were validated ex vivo in PBMCs from patients with MS treated with cladribine that have the potential to become treatment response biomarkers to this drug.

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“…As leptin and BDNF activate shared signaling pathways, such as PI3K and MAPK/ERK and some intermediary molecules, including SH2 and GRB2, leptin could induce positive feedback by increasing BDNF expression. In a recent report [ 126 ], 10 PD-related hub genes, including JAK2, ObRb and IRS2, among others, are involved in AMPK and leptin signaling.…”

Section: Functionality Of Leptin and Its Involvement In Pathologymentioning

confidence: 99%

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

Casado

Collado-Pérez

Frago

et al. 2023

IJMS

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Excess body weight is frequently associated with low-grade inflammation. Evidence indicates a relationship between obesity and cancer, as well as with other diseases, such as diabetes and non-alcoholic fatty liver disease, in which inflammation and the actions of various adipokines play a role in the pathological mechanisms involved in these disorders. Leptin is mainly produced by adipose tissue in proportion to fat stores, but it is also synthesized in other organs, where leptin receptors are expressed. This hormone performs numerous actions in the brain, mainly related to the control of energy homeostasis. It is also involved in neurogenesis and neuroprotection, and central leptin resistance is related to some neurological disorders, e.g., Parkinson’s and Alzheimer’s diseases. In peripheral tissues, leptin is implicated in the regulation of metabolism, as well as of bone density and muscle mass. All these actions can be affected by changes in leptin levels and the mechanisms associated with resistance to this hormone. This review will present recent advances in the molecular mechanisms of leptin action and their underlying roles in pathological situations, which may be of interest for revealing new approaches for the treatment of diseases where the actions of this adipokine might be compromised.

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Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease

Cited by 7 publications

References 46 publications

Gender differences in microRNA expression in levodopa-naive PD patients

Gender differences in microRNA expression in levodopa-naive PD patients

Molecular signature associated with cladribine treatment in patients with multiple sclerosis

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

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