A piRNA utilizes HILI and HIWI2 mediated pathway to down-regulate ferritin heavy chain 1 mRNA in human somatic cells

Balaratnam, Sumirtha; West, Nicole; Basu, Soumitra

doi:10.1093/nar/gky728

Cited by 24 publications

(25 citation statements)

References 78 publications

(100 reference statements)

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“…piRNAs have predominantly been linked to germ cell/stem cell development and maintenance and transposon regulation [12,13,14,15]. However, several studies have also demonstrated their gene regulatory potential in somatic cells [16,17]. Furthermore, the stability of piRNAs in body fluids has also opened up the possibility that piRNAs might serve as circulating biomarkers [18,19].…”

Section: Resultsmentioning

confidence: 99%

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Krishnan

Syed

Kang

et al. 2019

IJMS

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Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Toward the goal of informing T1D biomarker strategies, we profiled coding and noncoding RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under proinflammatory cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ. Total RNA and small RNA sequencing were performed from islet-derived exosomes to identify mRNAs, long noncoding RNAs, and small noncoding RNAs. RNAs with a fold change ≥1.3 and a p-value <0.05 were considered as differentially expressed. mRNAs and miRNAs represented the most abundant long and small RNA species, respectively. Each of the RNA species showed altered expression patterns with cytokine treatment, and differentially expressed RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis, and apoptosis. Taken together, our data identify RNAs that are dysregulated under cytokine stress in human islet-derived exosomes, providing a comprehensive catalog of protein coding and noncoding RNAs that may serve as potential circulating biomarkers in T1D.

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Section: Resultsmentioning

confidence: 99%

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Krishnan

Syed

Kang

et al. 2019

IJMS

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“…As mentioned above, chemical modifications of antagomiRs determine microRNA fate by targeting it for degradation or accumulation in heteroduplexes [115, 138–141]. Interestingly, possibilities of piRNA chemical modifications are much less well explored, despite the fact that naturally existing piRNAs incorporate the 3′-end 2′- O -methyl modification that protects them from RNases [184].…”

Section: Introductionmentioning

confidence: 99%

Editorial focus: understanding off-target effects as the key to successful RNAi therapy

Bartoszewski

Sikorski

2019

Cell Mol Biol Lett

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With the first RNA interference (RNAi) drug (ONPATTRO (patisiran)) on the market, we witness the RNAi therapy field reaching a critical turning point, when further improvements in drug candidate design and delivery pipelines should enable fast delivery of novel life changing treatments to patients. Nevertheless, ignoring parallel development of RNAi dedicated in vitro pharmacological profiling aiming to identify undesirable off-target activity may slow down or halt progress in the RNAi field. Since academic research is currently fueling the RNAi development pipeline with new therapeutic options, the objective of this article is to briefly summarize the basics of RNAi therapy, as well as to discuss how to translate basic research into better understanding of related drug candidate safety profiles early in the process.

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“…Second, piRNAs also regulate gene expression at the post-transcriptional level via alternative splicing or controlling mRNA stability, and RNA endonucleolytic cleavage or interaction with RNAs 54,55. In general, piRNAs target the transposon sequences found in the 3′-UTRs or 5′-UTRs of mRNAs, and piRNAs derived from pseudogenes and antisense transcripts also target the mRNA of the corresponding endogenous gene, resulting in mRNA deadenylation or degradation 15,56–58. Several studies have confirmed the relationship between piRNAs and their target mRNAs 56,59–61.…”

Section: Mechanisms Of Action Of Pirnasmentioning

confidence: 99%

<p>The emerging roles of PIWI-interacting RNA in human cancers</p>

Xiao

Hann

2019

CMAR

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PIWI-interacting RNAs (piRNAs) are a type of non-coding RNAs that interact with PIWI proteins, which are members of the argonaute family. Originally described in the germline, piRNAs are also expressed in human somatic cells in a tissue-specific manner. piRNAs are involved in spermatogenesis, germ stem-cell maintenance, silencing of transposon, epigenetic and genomic regulation and rearrangement. A large number of studies have demonstrated that expression of piRNAs is involved in many kinds of disease, including cancer. Abnormal expression of piRNAs is emerging as a critical player in cancer cell proliferation, apoptosis, invasion, and migration in vitro and in vivo. Functionally, piRNAs maintain genomic integrity by repressing the mobilization of transposable elements, and regulate the expression of downstream target genes via transcriptional or post-transcriptional mechanisms. Furthermore, altered expression of piRNAs in cancer is linked to clinical outcome, highlighting the important role that they may play as novel diagnostic and prognostic biomarkers, and as therapeutic targets for cancer therapy. In this review, we focus on the biogenesis and the functional roles of piRNAs in cancers, discuss emerging insights into the roles of piRNAs in the occurrence, progression, and treatment of cancers, reveal various mechanisms underlying piRNAs-mediated gene regulation, and highlight their potential clinical utilities as biomarkers as well as potential targets for cancer treatment.

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A piRNA utilizes HILI and HIWI2 mediated pathway to down-regulate ferritin heavy chain 1 mRNA in human somatic cells

Cited by 24 publications

References 78 publications

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Editorial focus: understanding off-target effects as the key to successful RNAi therapy

<p>The emerging roles of PIWI-interacting RNA in human cancers</p>

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