Epigenetic reactivation of <scp>LINE</scp>‐1 retrotransposon disrupts Nu<scp>RD</scp> corepressor functions and induces oncogenic transformation in human bronchial epithelial cells

Bojang, Pasano; Ramos, Kenneth S.

doi:10.1002/1878-0261.12329

Cited by 14 publications

(16 citation statements)

References 50 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A difference in transcription of these autonomous retrotransposons cannot only be induced by various chemical and biological stressors, but also has been observed in cancers, neurodegenerative disorders and autoimmune diseases [44–49]. This would be due to hypomethylation of CpG islands and chromatin rearrangements [50–52]. In addition, a qPCR analysis of human brain tissue showed a high variation in LINE-1 copy number expression between individuals, especially in the hippocampus, and differential expression between neurons [53, 54].…”

Section: Discussionmentioning

confidence: 99%

The validation of Short Interspersed Nuclear Elements (SINEs) as a RT-qPCR normalization strategy in a rodent model for temporal lobe epilepsy

et al. 2019

View full text Add to dashboard Cite

BackgroundIn gene expression studies via RT-qPCR many conclusions are inferred by using reference genes. However, it is generally known that also reference genes could be differentially expressed between various tissue types, experimental conditions and animal models. An increasing amount of studies have been performed to validate the stability of reference genes. In this study, two rodent-specific Short Interspersed Nuclear Elements (SINEs), which are located throughout the transcriptome, were validated and assessed against nine reference genes in a model of Temporal Lobe Epilepsy (TLE). Two different brain regions (i.e. hippocampus and cortex) and two different disease stages (i.e. acute phase and chronic phase) of the systemic kainic acid rat model for TLE were analyzed by performing expression analyses with the geNorm and NormFinder algorithms. Finally, we performed a rank aggregation analysis and validated the reference genes and the rodent-specific SINEs (i.e. B elements) individually via Gfap gene expression.ResultsGeNorm ranked Hprt1, Pgk1 and Ywhaz as the most stable genes in the acute phase, while Gusb and B2m were ranked as the most unstable, being significantly upregulated. The two B elements were ranked as most stable for both brain regions in the chronic phase by geNorm. In contrast, NormFinder ranked the B1 element only once as second best in cortical tissue for the chronic phase. Interestingly, using only one of the two algorithms would have led to skewed conclusions. Finally, the rank aggregation method indicated the use of the B1 element as the best option to normalize target genes, independent of the disease progression and brain region. This result was supported by the expression profile of Gfap.ConclusionIn this study, we demonstrate the potential of implementing SINEs -notably the B1 element- as a stable normalization factor in a rodent model of TLE, independent of brain region or disease progression.

show abstract

Section: Discussionmentioning

confidence: 99%

The validation of Short Interspersed Nuclear Elements (SINEs) as a RT-qPCR normalization strategy in a rodent model for temporal lobe epilepsy

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Some of the molecular phenomena related to L1‐RTP alteration induced by environmental factors are here briefly summarized. Alteration of methylation level within the L1 promoter CpG island. It was observed in cells subjected to treatment with arsenic (Paul et al ., ), lead (Wright et al ., ), nickel (Brocato and Costa, ), and B(a)P (Teneng et al ., ; Bojang Jr and Ramos, ). It was also observed in rats treated with METH (Moszczynska et al ., ).…”

Section: Brief Mentions Of the Molecular Mechanismsmentioning

confidence: 99%

Long INterspersed element‐1 mobility as a sensor of environmental stresses

Giorgi

2020

Environ and Mol Mutagen

View full text Add to dashboard Cite

Long INterspersed element (LINE-1, L1) retrotransposons are the most abundant transposable elements in the human genome, constituting approximately 17%. They move by a "copy-paste" mechanism, involving reverse transcription of an RNA intermediate and insertion of its cDNA copy at a new site in the genome. L1 retrotransposition (L1-RTP) can cause insertional mutations, alter gene expression, transduce exons, and induce epigenetic dysregulation. L1-RTP is generally repressed; however, a number of observations collected over about 15 years revealed that it can occur in response to environmental stresses. Moreover, emerging evidence indicates that L1-RTP can play a role in the onset of several neurological and oncological diseases in humans. In recent years, great attention has been paid to the exposome paradigm, which proposes that health effects of an environmental factor should be evaluated considering both cumulative environmental exposures and the endogenous processes resulting from the biological response. L1-RTP could be an endogenous process considered for this application. Here, we summarize the current understanding of environmental factors that can affect the retrotransposition of human L1 elements. Evidence indicates that L1-RTP alteration is triggered by numerous and various environmental stressors, such as chemical agents (heavy metals, carcinogens, oxidants, and drugs), physical agents (ionizing and non-ionizing radiations), and experiential factors (voluntary exercise, social isolation, maternal care, and environmental light/dark cycles). These data come from in vitro studies on cell lines and in vivo studies on transgenic animals: future investigations should be focused on physiologically relevant models to gain a better understanding of this topic.

show abstract

“…29 The silencing of LINE-1 is executed via DNA methylation through a complex process that involves assembly of nucleosome remodeling deacetylase (NuRD) corepressor complexes. 30 These repressive marks can be removed by aberrant endogenous cellular processes and/or exposure to agents that induce DNA damage or perturb the epigenome. 31 Reactivation of LINE-1 can reprogram the genome by causing insertion mutations or deletions that disrupt genome architecture and function.…”

Section: Long Interspersed Nuclear Element-1 As a Therapeutic Targetmentioning

confidence: 99%

Precision prevention: A focused response to shifting paradigms in healthcare

Ramos

Bowers

Tavera-Garcia

et al. 2019

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Human health and disease are defined at the intersection of molecules, environment, and lifestyle, which combined determine phenotypic outcomes. To date, most clinical applications in the precision medicine space have focused on DNA, with lesser attention given to the biology encoded by RNA molecules, or the complexity of biological regulation at the level of proteins and metabolites. The totality of this information must be integrated in ways that allow for implementation of knowledge-based health promotion and prevention strategies that can help address current limitations in healthcare delivery. This review describes recent advances in the development of diagnostic tools for early detection and stratification of individuals suffering from chronic obstructive pulmonary disease and their heightened risk for the development of lung malignancies. Impact statement The study of LINE-1 retroelements and their role in the pathogenesis of diseases of the lung such as COPD and lung cancer may provide valuable diagnostic and therapeutic tools to identify pre-emptively individuals at risk of pulmonary disease progression. Limited information is presently available on the role of LINE-1 in the regulation of disease phenotypes and the development of novel therapeutics designed to curtail LINE-1-mediated pathogenesis. Successful implementation of precision prevention strategies may help to spare those impacted by obstructive pulmonary disease from continued deterioration, while realizing significant cost savings and improved quality of healthcare.

show abstract

Epigenetic reactivation of LINE‐1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells

Cited by 14 publications

References 50 publications

The validation of Short Interspersed Nuclear Elements (SINEs) as a RT-qPCR normalization strategy in a rodent model for temporal lobe epilepsy

The validation of Short Interspersed Nuclear Elements (SINEs) as a RT-qPCR normalization strategy in a rodent model for temporal lobe epilepsy

Long INterspersed element‐1 mobility as a sensor of environmental stresses

Precision prevention: A focused response to shifting paradigms in healthcare

Contact Info

Product

Resources

About