Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Caenorhabditis elegans Parkinson’s Disease Model Overexpressing Human α-Synuclein and Influence of tdp-1

Shen, Linjing; Wang, Changliang; Chen, Liang; Wong, Garry

doi:10.3389/fnins.2021.600462

Cited by 15 publications

(19 citation statements)

References 79 publications

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“…These miRs can be detected in body fluids, such as blood [ 134 ], by applying a sensitive, cheap, and simple assay. Indeed, fluctuation in the expression of these circulating and tissue miRs concomitant with different diseases, including obesity [ 135 ], T2DM [ 136 ], cardiac disorder [ 65 ], cancer [ 137 ], aging [ 138 ], and neurodegenerative disorders such as Huntington’s disease (HD), Alzheimer’s disease (AD), and Parkinson’s disease (PD) has been identified [ 139 ].…”

Section: Extracellular Mirs As Disease Biomarkersmentioning

confidence: 99%

Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Kiran

Kumar

et al. 2021

Cells

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Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

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Section: Extracellular Mirs As Disease Biomarkersmentioning

confidence: 99%

Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Kiran

Kumar

et al. 2021

Cells

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“…While these associations suggest specific targets through which the piRNAs may act, validation of each specific biochemical step remains to be performed. Model organisms may thus help in this regard, and a study from our lab demonstrated dysregulation of specific miRNAs and piRNAs in a PD model [ 144 ]. Ultimately, the function piRNAs in blood extracellular vesicles might reveal information concerning cell–cell communication and disease progression.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Human Somatic piRNA Expression in Parkinson’s Disease Subtypes and Stages

Zhang

Wong

2022

IJMS

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Piwi interacting RNAs (piRNAs) are small non-coding single-stranded RNA species 20–31 nucleotides in size generated from distinct loci. In germline tissues, piRNAs are amplified via a “ping-pong cycle” to produce secondary piRNAs, which act in transposon silencing. In contrast, the role of somatic-derived piRNAs remains obscure. Here, we investigated the identity and distribution of piRNAs in human somatic tissues to determine their function and potential role in Parkinson’s disease (PD). Human datasets were curated from the Gene Expression Omnibus (GEO) database and a workflow was developed to identify piRNAs, which revealed 902 somatic piRNAs of which 527 were expressed in the brain. These were mainly derived from chromosomes 1, 11, and 19 compared to the germline tissues, which were from 15 and 19. Approximately 20% of somatic piRNAs mapped to transposon 3′ untranslated regions (UTRs), but a large proportion were sensed to the transcript in contrast to germline piRNAs. Gene set enrichment analysis suggested that somatic piRNAs function in neurodegenerative disease. piRNAs undergo dysregulation in different PD subtypes (PD and Parkinson’s disease dementia (PDD)) and stages (premotor and motor). piR-has-92056, piR-hsa-150797, piR-hsa-347751, piR-hsa-1909905, piR-hsa-2476630, and piR-hsa-2834636 from blood small extracellular vesicles were identified as novel biomarkers for PD diagnosis using a sparse partial least square discriminant analysis (sPLS-DA) (accuracy: 92%, AUC = 0.89). This study highlights a role for piRNAs in PD and provides tools for novel biomarker development.

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“…Another study published by Shen et al [174] used a worm model. Transgenic C. elegans nematodes overexpressing human α-syn wild type (WT) and the A53T mutant (HASN WT OX andHASN A53T OX) were crossbred with C. elegans with knockout (KO) of the human TDP-43-like protein tdp-1 (tdp-1 KO).…”

Section: Pirnas In a Pd Nematode Modelmentioning

confidence: 99%

The role of noncoding RNAs in Parkinson’s disease: biomarkers and associations with pathogenic pathways

et al. 2021

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The discovery of various noncoding RNAs (ncRNAs) and their biological implications is a growing area in cell biology. Increasing evidence has revealed canonical and noncanonical functions of long and small ncRNAs, including microRNAs, long ncRNAs (lncRNAs), circular RNAs, PIWI-interacting RNAs, and tRNA-derived fragments. These ncRNAs have the ability to regulate gene expression and modify metabolic pathways. Thus, they may have important roles as diagnostic biomarkers or therapeutic targets in various diseases, including neurodegenerative disorders, especially Parkinson’s disease. Recently, through diverse sequencing technologies and a wide variety of bioinformatic analytical tools, such as reverse transcriptase quantitative PCR, microarrays, next-generation sequencing and long-read sequencing, numerous ncRNAs have been shown to be associated with neurodegenerative disorders, including Parkinson’s disease. In this review article, we will first introduce the biogenesis of different ncRNAs, including microRNAs, PIWI-interacting RNAs, circular RNAs, long noncoding RNAs, and tRNA-derived fragments. The pros and cons of the detection platforms of ncRNAs and the reproducibility of bioinformatic analytical tools will be discussed in the second part. Finally, the recent discovery of numerous PD-associated ncRNAs and their association with the diagnosis and pathophysiology of PD are reviewed, and microRNAs and long ncRNAs that are transported by exosomes in biofluids are particularly emphasized.

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Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Caenorhabditis elegans Parkinson’s Disease Model Overexpressing Human α-Synuclein and Influence of tdp-1

Cited by 15 publications

References 79 publications

Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Dysregulation of Human Somatic piRNA Expression in Parkinson’s Disease Subtypes and Stages

The role of noncoding RNAs in Parkinson’s disease: biomarkers and associations with pathogenic pathways

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