Bioinformatic analysis of a microRNA regulatory network in Huntington’s disease

Wang, Zhimin; Dong, Xiaoyu; Cong, Shuyan

doi:10.31083/j.jin.2020.04.203

Cited by 12 publications

(6 citation statements)

References 48 publications

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“…Huntington disease is a hereditary neurodegenerative condition which impacts in early forties and fifties. 24 , 79 Dysregulation of possible biomarkers has recently been found to be linked with neurological and neurodegenerative diseases, 80 , 81 and several studies have looked into the implications of biomolecular activities in patients with HD. 27 , 82 - 85 Omics-based approaches are currently being used more often in biomedicine and systemic biology studies, and they have proven to be a helpful resource for deciphering disease pathogenesis, discovering molecular pathways, and determining biomarkers for various diseases.…”

Section: Discussionmentioning

confidence: 99%

“… 20 , 22 Due to prolonged CAG repeat, HTT protein with an enlarged polyglutamine tract is produced, resulting in pathogenic HTT protein residues that are immune to the protein cycle, leading to cellular toxicity. 23 , 24 Most HD patients have motor-involved problems, a small percentage (15%) establish clinically relevant psychological disease first and hence have a mental diagnosis before the start of movement disorder. 20 , 25 Huntington disease is associated with extremely selective deterioration of the corpus striatum which is a brain region with no noticeable abnormalities in peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

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A Comprehensive Bioinformatics Approach to Identify Molecular Signatures and Key Pathways for the Huntington Disease

Meem,

Khan,

Mredul

et al. 2023

Bioinform Biol Insights

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Huntington disease (HD) is a degenerative brain disease caused by the expansion of CAG (cytosine-adenine-guanine) repeats, which is inherited as a dominant trait and progressively worsens over time possessing threat. Although HD is monogenetic, the specific pathophysiology and biomarkers are yet unknown specifically, also, complex to diagnose at an early stage, and identification is restricted in accuracy and precision. This study combined bioinformatics analysis and network-based system biology approaches to discover the biomarker, pathways, and drug targets related to molecular mechanism of HD etiology. The gene expression profile data sets GSE64810 and GSE95343 were analyzed to predict the molecular markers in HD where 162 mutual differentially expressed genes (DEGs) were detected. Ten hub genes among them ( DUSP1, NKX2-5, GLI1, KLF4, SCNN1B, NPHS1, SGK2, PITX2, S100A4, and MSX1) were identified from protein-protein interaction (PPI) network which were mostly expressed as down-regulated. Following that, transcription factors (TFs)-DEGs interactions (FOXC1, GATA2, etc), TF-microRNA (miRNA) interactions (hsa-miR-340, hsa-miR-34a, etc), protein-drug interactions, and disorders associated with DEGs were predicted. Furthermore, we used gene set enrichment analysis (GSEA) to emphasize relevant gene ontology terms (eg, TF activity, sequence-specific DNA binding) linked to DEGs in HD. Disease interactions revealed the diseases that are linked to HD, and the prospective small drug molecules like cytarabine and arsenite was predicted against HD. This study reveals molecular biomarkers at the RNA and protein levels that may be beneficial to improve the understanding of molecular mechanisms, early diagnosis, as well as prospective pharmacologic targets for designing beneficial HD treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Comprehensive Bioinformatics Approach to Identify Molecular Signatures and Key Pathways for the Huntington Disease

Meem,

Khan,

Mredul

et al. 2023

Bioinform Biol Insights

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“…Shaohong Isaac Peng, 1,2,8 Zhefan Stephen Chen, 1,2,8 Lok I Leong, 1,2 Xiao Lin, 2 Yuming Wei, 1,2 Alex Chun Koon, 1,2 Junzhe Huang, 3 Jacquelyne Ka-Li Sun, 2 Kin Ming Kwan, 2,4,5 Hei-Man Chow, 2,7 Ho Ko, 3,6 Ting-Fung Chan, 2,4,7 and Ho Yin Edwin Chan…”

Section: Declaration Of Interestsunclassified

“…Several studies have reported that microRNA (miRNA) homeostasis is perturbed in polyQ diseases, 4 including HD. 5,6,7 miRNAs are small non-coding RNAs and are components of the RNA-induced silencing complex (RISC), which guides the post-transcriptional silencing of mRNA targets. 8 Supplementation with miRNAs has been shown to be a potential therapeutic strategy against HD in mice.…”

Section: Introductionmentioning

confidence: 99%

Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5

Chan,

Peng,

Chen

et al. 2024

Preprint

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MicroRNAs (miRNAs) are small non-coding RNAs responsible for RNA silencing and the posttranscriptional regulation of gene expression. Poly(A) RNA polymerase D5 (PAPD5) catalyzes the addition of adenosine to the 3′ end of miRNAs, which promotes their subsequent degradation. In this study, we demonstrated that the Yin Yang 1 (YY1) protein, a transcriptional repressor of PAPD5, was recruited to both RNA foci and protein aggregates, which caused the upregulation of PAPD5 expression in Huntington’s disease (HD). We further identified a subset of PAPD5-regulated miRNAs with downregulated levels in our disease model. We focused on miR-504-5p and miR-7-5p and found that their reduction caused the activation of the TAB1/2-mediated TAK1–MKK4–JNK pro-apoptotic pathway. We further showed that this pathway was activated in HD patient induced pluripotent stem cell-derived neurons. In addition, we discovered that a small molecule PAPD5 inhibitor, BCH001, mitigated the cell death and neurodegeneration in our disease models. This study highlights the importance of PAPD5-mediated miRNA dysfunction in the pathogenesis of HD and as a potential therapeutic direction for the disease.

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“…A smaller number of studies have explored the miRNA profiles in HD. These profiles are found in the brain [ 159 , 160 , 161 ], plasma [ 162 ], and CSF [ 163 ] of HD patients and in the brain of HD mouse models [ 164 , 165 , 166 , 167 ]. No common miRNAs are found between the profiles performed in HD patients, but there are two miRNAs, miR-10b-5p and miR-10a-5p, that are upregulated in the brain of both HD patients and mouse models.…”

Section: Epigenetic Changes In Prion-like Diseasesmentioning

confidence: 99%

Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives

Hernaiz

Toivonen²,

Bolea³

et al. 2022

IJMS

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Prion diseases are transmissible spongiform encephalopathies (TSEs) caused by a conformational conversion of the native cellular prion protein (PrPC) to an abnormal, infectious isoform called PrPSc. Amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s, and Huntington’s diseases are also known as prion-like diseases because they share common features with prion diseases, including protein misfolding and aggregation, as well as the spread of these misfolded proteins into different brain regions. Increasing evidence proposes the involvement of epigenetic mechanisms, namely DNA methylation, post-translational modifications of histones, and microRNA-mediated post-transcriptional gene regulation in the pathogenesis of prion-like diseases. Little is known about the role of epigenetic modifications in prion diseases, but recent findings also point to a potential regulatory role of epigenetic mechanisms in the pathology of these diseases. This review highlights recent findings on epigenetic modifications in TSEs and prion-like diseases and discusses the potential role of such mechanisms in disease pathology and their use as potential biomarkers.

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Bioinformatic analysis of a microRNA regulatory network in Huntington’s disease

Cited by 12 publications

References 48 publications

A Comprehensive Bioinformatics Approach to Identify Molecular Signatures and Key Pathways for the Huntington Disease

A Comprehensive Bioinformatics Approach to Identify Molecular Signatures and Key Pathways for the Huntington Disease

Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5

Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives

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