Human Endogenous Retroviruses in Neurological Diseases

Küry, Patrick; Nath, Avindra; Créange, Alain; Dolei, Antonina; Marche, Patrice N.; Gold, Julian; Giovannoni, Gavin; Hartung, Hans‐Peter; Perron, Hervé

doi:10.1016/j.molmed.2018.02.007

Cited by 235 publications

(244 citation statements)

References 104 publications

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“…Human endogenous retroviruses (HERVs) are relics of the infective retrovirus integrated into the human genome, accounting for approximately 5%‐8% of the human genome, including at least 31 families . They participate in the regulation of various physiological and pathological activities in humans through different pathways . Most of the HERVs genes lose their transcriptional ability due to mutation or partial deletion, but some genes remain intact as open reading frames and can be translated into functional proteins, such as Syncytin 1.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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Syncytin 1 is considered as an oncogene in various malignant tumors, but its effect on non‐small cell lung cancer (NSCLC) has not been reported. We investigated the specific role of Syncytin 1 on NSCLC through the transfection of Syncytin 1 knockdown or overexpression plamids in A549 cells. Our results proved that knockdown of Syncytin 1 inhibited the proliferation, and blocked the cell cycle on G1 phase by inhibiting the expression of Nusap1, Cyclin D1, CDK6, and CDK4. Cell cycle arrest also leaded to increased apoptosis in Syncytin 1 knockdown cells. Suppression of Syncytin 1 inhibited the migration and invasion, as well as the expressions of epithelial‐mesenchymal transition (EMT) makers, N‐cadherin, β‐catenin, and Vimentin, indicating that Syncytin 1 knockdown inhibited the metastasis via reversing the EMT process in A549 cells. The phosphorylation levels of Akt, mTOR, and Erk1/2 were all decreased in Syncytin 1 knockdown cells, suggesting the signaling pathways by which Syncytin 1 operated as an oncogene in NSCLC. Moreover, the underexpression of transcription factor SP1 downregulated the Syncytin 1 expression in A549 cells. The rescue experiment of Syncytin 1 in SP1 knockdown cells further proved that Syncytin 1 could block the inhibition of cell growth induced by SP1 knockdown. In conclusion, knockdown of SP1/Syncytin1 axis inhibited the progression of NSCLC by the reversion of tumor epithelial‐mesenchymal transition process and suppression of Akt and Erk signaling pathways, suggesting that they are potential targets for targeted therapy of NSCLC.

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Section: Introductionmentioning

confidence: 99%

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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“…Likewise, an earlier study has reported that transposons are not an abundant source of enhancers in the mammalian neocortex (Emera et al , ). We speculate that keeping HERV sequences silent in brain may be of particular importance because of the several neurological diseases associated with HERV expression in that tissue, including multiple sclerosis, amyotrophic lateral sclerosis, and chronic inflammatory demyelinating polyradiculoneuropathy (Küry et al , ). We note also that the low usage of HERVs in pancreatic islets is yet another similarity between this tissue and brain tissues, which in numerous studies have been reported to share transcriptional programs (Arntfield & van der Kooy, ).…”

Section: Discussionmentioning

confidence: 99%

Expression of endogenous retroviruses reflects increased usage of atypical enhancers in T cells

et al. 2019

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Several autoimmune diseases including multiple sclerosis (MS) cause increased transcription of endogenous retroviruses (HERVs) normally repressed by heterochromatin. In parallel, HERV‐derived sequences were reported to drive gene expression. Here, we have examined a possible link between promoter and enhancer divergent transcription and the production of HERV transcripts. We find that HERV‐derived sequences are in general counter‐selected at regulatory regions, a counter‐selection that is strongest in brain tissues while very moderate in stem cells. By exposing T cells to the pesticide dieldrin, we further found that a series of HERV‐driven enhancers otherwise active only at stem cell stages can be reactivated by stress. This in part relies on peptidylarginine deiminase activity, possibly participating in the reawakening of silenced enhancers. Likewise, usage of HERV‐driven enhancers was increased in myelin‐reactive T cells from patients with MS, correlating with activation of nearby genes at several sites. Altogether, we propose that HERV‐driven enhancers constitute a reservoir of auxiliary enhancers transiently induced by stress while chronically active in diseases like MS.

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“…Retroviruses are associated with a broad spectrum of neurological disorders (3)(4)(5)(6)(7)(8)(9). HIV has been associated with an ALS-like motor neuron disease in over 30 patients (3)(4)(5)(6).…”

Section: Mechanismsmentioning

confidence: 99%

“…HERV expression is also increased in a number of other neurological (7,28,29) and non-neurological diseases, such as cancer (30). Furthermore, some think that HERVs may play beneficial roles in the pathophysiology of certain diseases (31); however, this may not be the case in all diseases as research on multiple sclerosis has suggested a pathogenic role for HERVs (32,33).…”

Section: Mechanismsmentioning

confidence: 99%

ALSUntangled 45: Antiretrovirals

2018

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Human Endogenous Retroviruses in Neurological Diseases

Cited by 235 publications

References 104 publications

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Expression of endogenous retroviruses reflects increased usage of atypical enhancers in T cells

ALSUntangled 45: Antiretrovirals

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