Elucidating the role of a shared lncRNA-miRNA-mRNA network in exacerbating Parkinson’s disease symptoms in the context of COVID-19 infection

Background and objectives

Parkinson’s disease (PD) is a common neurodegenerative disorder with unclear molecular mechanisms. Noncoding RNAs, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have been identified as critical regulators of gene expression. This study aimed to investigate the triple network of lncRNA-miRNA-mRNA, known as competing endogenous RNAs (ceRNAs), and to identify essential lncRNAs that regulate PD-related gene expression through their target miRNAs. The study also identified a common triple network between COVID-19 and PD that may contribute to exacerbating PD symptoms.

 

Methods

A bioinformatics approach was employed to construct a PD ceRNA network using common PD genes, miRNAs and lncRNAs with the highest interaction with their targets. Also, a PD-COVID-19 triple network was constructed by integrating PD network nodes into the COVID-19 network.

 

Results

The PD ceRNA network comprised 34 nodes, including 12 lncRNAs, 16 miRNAs with interconnections and six mRNAs, some of which were related to COVID-19. The network showed parallel expression of the SNCA and PARK7 genes as well as the NEAT1 and MALAT1 lncRNAs in both PD and COVID-19.

 

Conclusions

In this study, two regulatory networks were constructed. The first network consisted of six mRNAs (PINK1, LRRK2, PARK7, SNCA, PRKN and ATP13A2), 16 miRNAs (hsa-miR-26b-5p, hsa-miR-7-5p, hsa-miR-335-5p, hsa-miR-181a-5p, hsa-miR-582-5p, hsa-miR-148b-3p, hsa-miR-144, hsa-miR-221, hsa-miR-488, hsa-miR-27a-3p, miR-27b-3p, hsa-miR-34c, hsa-miR-92a-3p, hsa-miR-3929, hsa-miR-30c-5p and hsa-miR-24-3p) and 12 lncRNAs (MALAT1, NEAT1, RP11-314B1.2, XIST, IPW, LINC00938, MEG3, CASC7, RP11-361F15.2, RP11-391M1.4, LINC01355 and RP11-819C21.1), which may serve as potential biomarkers for PD diagnosis and progression. Therefore, the findings of this network should be explored in future investigations of PD.

 

The second network was designed using the first network and nodes involved in COVID-19. This network comprised NEAT1 and MALAT1 as important lncRNAs that interacted with eight candidate miRNAs (hsa-miR-148b-3p, hsa-miR-3929, hsa-miR-26b-5p, hsa-miR-144, hsa-miR-34c, hsa-miR-221, hsa-miR-488 and hsa-miR-7-5p) and regulated SNCA and PARK7 genes, thus affecting COVID-19. In this study, based on bioinformatics studies, we found that the expression levels of the SNCA and PARK7 genes in both PD disease and COVID-19 infection were upregulated, as were the expression levels of NEAT1 and MALAT1. Therefore, the parallel expression of these mRNAs and lncRNAs in PD and COVID-19 leads to worsened PD symptoms in the presence of COVID-19. Our study provides insights into specific genes that may serve as biomarkers for PD and highlights the potential interaction between PD and COVID-19. These findings have implications for early diagnosis, disease monitoring, and understanding the impact of COVID-19 on PD symptoms. Further research and validation are needed to confirm these findings and explore their clinical applications.

 

Full text

https://www.xiahepublishing.com/1555-3884/GE-2023-00103

 

The study was recently published in the Gene Expression.

Gene Expression (GE) is an open-access journal. It was launched in 1991 by Chicago Medical School Press, and transferred to Cognizant Communication Corporation in 1994. From August 2022, GE is published by Xia & He Publishing Inc.   

GE publishes peer-reviewed and high-quality original articles, reviews, editorials, commentaries, and opinions on its primary research topics including cell biology, molecular biology, genes, and genetics, especially on the cellular and molecular mechanisms of human diseases. 

GE has been indexed in Medline (1991-2021), Scopus, Biological Abstracts, Biosis Previews, ProQuest, etc.

 

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