Potential of Long Non-Coding RNAs in Age-Related Macular Degeneration

Błasiak, Janusz; Hyttinen, Juha M. T.; Szczepańska, Joanna; Pawłowska, Elżbieta

doi:10.3390/ijms22179178

Cited by 15 publications

(6 citation statements)

References 106 publications

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“…97 Overexpression of PWRN2, a Prader-Willi region non-protein-coding RNA 2, has been associated with in age-related macular degeneration. 98 MARCHF10 is a E3 ubiquitin-protein ligase, a class of molecules implicated in memory formation, recovery from stroke and several neurological diseases. 99 We replicated our VaD signals using EADB data (Table 3).…”

Section: Discussionmentioning

confidence: 99%

A meta-analysis of genome-wide association studies identifies new genetic loci associated with all-cause and vascular dementia

Fongang

Sargurupremraj²,

Jian³

et al. 2022

Preprint

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Dementia is multifactorial with Alzheimer (AD) and vascular (VaD) pathologies making the largest contributions. Genome-wide association studies (GWAS) have identified over 70 genetic risk loci for AD but the genomic determinants of other dementias, including VaD remain understudied. We hypothesize that common forms of dementia will share genetic risk factors and conducted the largest GWAS to date of "all-cause dementia" (ACD) and examined the genetic overlap with VaD. Our dataset includes 809,299 individuals from European, African, Asian, and Hispanic ancestries with 46,902 and 8,702 cases of ACD and VaD, respectively. We replicated known AD loci at genome-wide significance for both ACD and VaD and conducted bioinformatic analyses in prioritizing genes that are functionally relevant and shared with closely related traits and risk factors. For ACD, novel loci were associated with energy transport throughout the brain (SEMA4D), neuronal excitability (ANO3), amyloid plaques deposition in the brain (RBFOX1), and MRI markers of small vessel disease (HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). In addition to the genetic overlap with neurodegenerative processes, genetic risk loci for ACD exhibited overlap with vascular risk factors (Type-II diabetes, blood pressure, lipid levels) and MRI markers of cerebral small vessel disease (cSVD). Our study identified genetic risk loci underlying ACD and VaD that point to the involvement of specific biological pathways and highlights their genetic overlap with vascular risk factors and MRI markers of cSVD. These novel insights could lead to new prevention and treatment strategies.

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Section: Discussionmentioning

confidence: 99%

A meta-analysis of genome-wide association studies identifies new genetic loci associated with all-cause and vascular dementia

Fongang

Sargurupremraj²,

Jian³

et al. 2022

Preprint

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“…Therefore, most transcripts cannot be translated into proteins which are de ned as ncRNAs. The ncRNAs contain various lncRNAs and miRNAs with a length of more than 200nt [23] and 22nt [24] , respectively.…”

Section: Discussionmentioning

confidence: 99%

Construction of a macula-specific lncRNA-miRNA-mRNA network in age- related macular degeneration patients

Chen

Yue

et al. 2022

Preprint

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Background:Age-related macular degeneration (AMD) is the primary cause of visual impairment among the elderly. It mainly affects the macular region of the fundus oculi. Studies have shown that macular and extramacular region's gene expression differs considerably. This may be the reason for regional specificity and different phenotypic outcomes of the AMD. The non-coding RNA (ncRNAs) is a RNAs that cannot encode proteins in the human transcribed genome. However, they are involved in many life events as regulatory molecules. NcRNAs were identified to play a vital role in AMD. But the molecular mechanism underlying ncRNAs in AMD remains unclear. In the current study, we explored the differences in the macular and extramacular regions of the retina gene expression in AMD patients. We investigated the function of ncRNAs by constructing the lncRNA-miRNA-mRNA network.Results:A total of 4491 DE-mRNAs and 18 DE-lncRNAs were discovered in the macular and the retina region of the retina of AMD patients. In the lncRNA-miRNA-mRNA network, 18 lncRNAs, 41 miRNAs, and 404 mRNAs were established through target gene prediction. Co-expression analysis showed that 51 pairs of lncRNAs and mRNAs in the lncRNA-miRNA-mRNA network had a positive co-expression. GO and KEGG pathway analysis indicated that mRNAs involved in the lncRNA-miRNA-mRNA network were mainly enriched in the apoptotic signaling pathway, negative regulation of nitrogen compound metabolic process, cellular response to chemical stimulus, and MAPK signaling pathway, endocytosis, PI3K-Akt signaling pathway, cellular senescence, hepatitis, axon guidance, microRNAs in cancer, mTOR signaling pathway, AMPK signaling pathway, and longevity regulating pathway. In addition, DO enrichment indicated that 18 DE-lncRNAs were enriched in 266 diseases.Conclusions:In this study, we constructed the lncRNA-miRNA-mRNA network consisting of 18 lncRNAs, 41 miRNAs, and 404 mRNAs. In addition, 51 pairs of lncRNAs and mRNAs presented a positive co-expression relationship.

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“…The fundamental function of lncRNAs is the regulation of gene expression that can be performed directly or indirectly in cis or trans. lncRNAs may form base pairs with a complementary fragment of mRNA, impeding its translation—the antisense function [ 115 ]. lncRNAs recruit and/or guide transcription factors to regulate the transcription of the target gene—the guide function.…”

Section: Epigenetic Connections Of Cgrpmentioning

confidence: 99%

Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine

Fila

Sobczuk

Pawłowska

et al. 2022

IJMS

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The calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of several pain-related syndromes, including migraine. Targeting CGRP and its receptor by their antagonists and antibodies was a breakthrough in migraine therapy, but the need to improve efficacy and limit the side effects of these drugs justify further studies on the regulation of CGRP in migraine. The expression of the CGRP encoding gene, CALCA, is modulated by epigenetic modifications, including the DNA methylation, histone modification, and effects of micro RNAs (miRNAs), circular RNAs, and long-coding RNAs (lncRNAs). On the other hand, CGRP can change the epigenetic profile of neuronal and glial cells. The promoter of the CALCA gene has two CpG islands that may be specifically methylated in migraine patients. DNA methylation and lncRNAs were shown to play a role in the cell-specific alternative splicing of the CALCA primary transcript. CGRP may be involved in changes in neural cytoarchitecture that are controlled by histone deacetylase 6 (HDAC6) and can be related to migraine. Inhibition of HDAC6 results in reduced cortical-spreading depression and a blockade of the CGRP receptor. CGRP levels are associated with the expression of several miRNAs in plasma, making them useful peripheral markers of migraine. The fundamental role of CGRP in inflammatory pain transmission may be epigenetically regulated. In conclusion, epigenetic connections of CGRP should be further explored for efficient and safe antimigraine therapy.

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Potential of Long Non-Coding RNAs in Age-Related Macular Degeneration

Cited by 15 publications

References 106 publications

A meta-analysis of genome-wide association studies identifies new genetic loci associated with all-cause and vascular dementia

A meta-analysis of genome-wide association studies identifies new genetic loci associated with all-cause and vascular dementia

Construction of a macula-specific lncRNA-miRNA-mRNA network in age- related macular degeneration patients

Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine

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