De novo 1Mb interstitial deletion of 8p22 in a patient with slight mental retardation and speech delay

Piovani, Giovanna; Savio, Giulia; Traversa, Michele; Pilotta, Alba; Petro, Giuseppina De; Barlati, Sergio; Magri, Chiara

doi:10.1186/1755-8166-7-25

Cited by 12 publications

(8 citation statements)

References 13 publications

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“…Among the dysregulated genes in excitatory neurons, we found altered expression of several lncRNAs and protein coding genes (Table EV2), many of which are linked to neurological disorders. Notably, we observed reduced expression of Hecw2 , a ubiquitin ligase linked to neurodevelopmental delay (Berko et al , 2017) and Sgcz , a transmembrane protein linked to mental retardation (Piovani et al , 2014) (Fig 4E). We also found transcriptional alterations in astrocytes and oligodendrocytes (Fig 4F and G), two additional cell types in which Emx1 is expressed during brain development and therefore should lack Trim28 expression.…”

Section: Resultsmentioning

confidence: 72%

Activation of endogenous retroviruses during brain development causes an inflammatory response

et al. 2021

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Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV-derived proteins in aggregate-like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.

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Section: Resultsmentioning

confidence: 72%

Activation of endogenous retroviruses during brain development causes an inflammatory response

et al. 2021

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“…Among the dysregulated genes in excitatory neurons, we found altered expression of several lncRNAs and protein-coding genes. Notably, we observed reduced expression of Hecw2, a ubiquitin ligase linked to neurodevelopmental delay (Berko et al, 2017) and Sgcz, a transmembrane protein linked to mental retardation (Piovani et al, 2014) (Fig 4e). We also found transcriptional alterations in astrocytes and oligodendrocytes (Fig 4f-g), two additional cell types in which Emx1 is expressed during brain development and therefore should lack Trim28 expression.…”

Section: Single-nuclei Rna-seq Analysis Of Erv-expressing Brain Tissuementioning

confidence: 86%

Activation of endogenous retroviruses during brain development causes neuroinflammation

Jönsson

Garza

Sharma

et al. 2020

Preprint

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AbstractEndogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for neuroinflammation, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERV expression in excitatory neurons in the adult brain. Neuronal ERV expression was linked to inflammation, including activated microglia, and aggregates of ERV-derived proteins. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in neuroinflammation.

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“…The host gene SGCZ of miR-383 is located on chr8p22 ( 34 ). It has been reported that a common region of LOH at the chr8p22 locus is related to breast cancer and prostate cancer ( 18 , 35 ), and the present study also confirmed that the low expression of miR-383 in lung adenocarcinoma tissues was related to the deletion of this locus.…”

Section: Discussionmentioning

confidence: 99%

miR‑383 increases the cisplatin sensitivity of lung adenocarcinoma cells through inhibition of the RBM24‑mediated NF‑κB signaling pathway

Sun

Yang

et al. 2021

Int J Oncol

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The expression of microRNA-383 (miR-383) is downregulated in a variety of tumor tissues, and it exhibits antiproliferative activity in non-small cell lung cancer cells. In the present study, an association between the downregulation of miR-383 expression and the deletion of chr8p22 in patients with lung adenocarcinoma was identified. The promoting effect of miR-383 on cisplatin sensitivity was verified both in vivo and in vitro. Additionally, it was revealed that the expression of RNA binding motif protein 24 (RBM24) protein was regulated by and negatively correlated with miR-383 expression. Ectopic expression of RBM24 or inhibition of miR-383 decreased the chemosensitivity of parental A549 cells, whereas knockdown of RBM24 in cisplatin-resistant A549 cells increased chemosensitivity. Mechanistically, miR-383 interfered with the activation of nuclear factor κB (NF-κB) signaling through repression of RBM24-mediated phosphorylation of Rel-like domain-containing protein A and inhibitor α of NF-κB. Taken together, the downregulation of miR-383 induced RBM24 expression, which was mediated through the activation of NF-κB signaling, to contribute to chemotherapy resistance in lung adenocarcinoma cells. The results of the present study highlight potential therapeutic targets for the clinical reversal of the chemotherapy resistance in lung adenocarcinoma.

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De novo 1Mb interstitial deletion of 8p22 in a patient with slight mental retardation and speech delay

Cited by 12 publications

References 13 publications

Activation of endogenous retroviruses during brain development causes an inflammatory response

Activation of endogenous retroviruses during brain development causes an inflammatory response

Activation of endogenous retroviruses during brain development causes neuroinflammation

miR‑383 increases the cisplatin sensitivity of lung adenocarcinoma cells through inhibition of the RBM24‑mediated NF‑κB signaling pathway

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