PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells

Taxiarchis, Apostolos; Mahdessian, Hovsep; Silveira, Angela; Hooft, Ferdinand M. van’t

doi:10.1194/jlr.m090928

Cited by 13 publications

(6 citation statements)

References 127 publications

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“…The specificity of atglistatin to human ATGL has been controversial [69]. However, our results were very similar to those with siRNA knockdown showing lipid droplet accumulation and increased migration, supporting the specificity of the inhibitor in our human NPC cell line model in line with studies in several other human systems [42–44,63,70,71].…”

Section: Discussionsupporting

confidence: 88%

“…Then, cells were cultured in the presence or absence of 150 lM 1-butanol (281549; Sigma-Aldrich) or 30 lM atglistatin (SML1075; Sigma-Aldrich). Atglistatin was originally discovered as an inhibitor of ATGL in mice, but has later been shown to also specifically inhibit human ATGL [41][42][43][44][45]. The widths of the gaps were evaluated again 8-15 h later.…”

Section: Migration Assaymentioning

confidence: 99%

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Downregulation of adipose triglyceride lipase by EB viral‐encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma

et al. 2020

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NNE normal nasopharyngeal epithelium EIF4E eukaryotic translation initiation factor 4E gene LC-MC liquid chromatography-mass spectrometry PLS-DA partial least squares-discriminant analysis OCR oxygen consumption rate ECAR extracellular acidification rate FCCP carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone IHC Immunohistochemistry siRNA small interfering RNA ROS reactive oxygen species PEDF pigment epithelium-derived factor

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Section: Discussionsupporting

confidence: 88%

Section: Migration Assaymentioning

confidence: 99%

Downregulation of adipose triglyceride lipase by EB viral‐encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma

et al. 2020

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“…The MALAT1-mitoTracker merged area of each field was quantified using the ImageJ and Particle Analysis Plugin. 18,19 The quantitative co-localization was observed between MALAT1 and mitochondria, with Rcoloc values of 0.73 ± 0.03 for commercial antisense oligonucleotide probes and 0.61 ± 0.12 for single-stranded DNA probes. As expected, the colocalization signal of MALAT1 was decreased in cells that were transfected with shMALAT1 lentivirus (Figure S4).…”

Section: Nuclear-encoded Lncrna Malat1 Is Aberrantly Enriched In the Mitochondria Of Hepatoma Cellsmentioning

confidence: 99%

Nuclear-Encoded lncRNA MALAT1 Epigenetically Controls Metabolic Reprogramming in HCC Cells through the Mitophagy Pathway

Zhao

Zhou

et al. 2021

Molecular Therapy - Nucleic Acids

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Mitochondrial dysfunction is a metabolic hallmark of cancer cells. In search of molecular factors involved in this dysregulation in hepatocellular carcinoma (HCC), we found that the nuclear-encoded long noncoding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was aberrantly enriched in the mitochondria of hepatoma cells. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we showed that MALAT1 interacted with multiple loci on mitochondrial DNA (mtDNA), including D-loop, COX2, ND3, and CYTB genes. MALAT1 knockdown induced alterations in the CpG methylation of mtDNA and in mitochondrial transcriptomes. This was associated with multiple abnormalities in mitochondrial function, including altered mitochondrial structure, low oxidative phosphorylation (OXPHOS), decreased ATP production, reduced mitophagy, decreased mtDNA copy number, and activation of mitochondrial apoptosis. These alterations in mitochondrial metabolism were associated with changes in tumor phenotype and in pathways involved in cell mitophagy, mitochondrial apoptosis, and epigenetic regulation. We further showed that the RNA-shuttling protein HuR and the mitochondria transmembrane protein MTCH2 mediated the transport of MALAT1 in this nuclear-mitochondrial crosstalk. This study provides the first evidence that the nuclear genome-encoded lncRNA MALAT1 functions as a critical epigenetic player in the regulation of mitochondrial metabolism of hepatoma cells, laying the foundation for further clarifying the roles of lncRNAs in tumor metabolic reprogramming.

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“…Article (Taxiarchis et al, 2019). In terms of immunity, expression changes in CD151, PIDD1, and DPP9-genes involved in immune cell activation and NF-kB-mediated immune response (Okondo et al, 2017;Rocha-Perugini et al, 2014;Tinel et al, 2007)-were associated with two distinct COVID-19 hg-replicated SNPs (rs3934992, rs12610495).…”

Section: Ll Open Access Isciencementioning

confidence: 99%

Phenome-wide and expression quantitative trait locus associations of coronavirus disease 2019 genetic risk loci

et al. 2021

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While several genes and clinical traits have been associated with higher risk of severe COVID-19, how host genetic variants may interact with these parameters and contribute to severe disease is still unclear. Herein, we performed phenome-wide association study (PheWAS), tissue and immune-cell specific expression/splicing quantitative trait loci (eQTL/sQTL), and colocalization analyses for genetic risk loci suggestively associated with severe COVID-19 with respiratory failure. Thirteen phenotypes/traits were associated with the severe COVID-19-associated loci at the genome-wide significance threshold, including monocyte counts, fat metabolism traits, and fibrotic idiopathic interstitial pneumonia. In addition, we identified tissue and immune subtype-specific eQTL associations affecting 48 genes, including several that may directly impact host immune responses, colocalized with the severe COVID-19 GWAS associations, and showed altered expression in single-cell transcriptomes. Collectively, our work demonstrates that host genetic variations associated with multiple genes and traits show genetic pleiotropy with severe COVID-19 and may inform disease etiology.

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PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells

Abstract: Hooft FV. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content.

Cited by 13 publications

References 127 publications

Downregulation of adipose triglyceride lipase by EB viral‐encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma

Downregulation of adipose triglyceride lipase by EB viral‐encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma

Nuclear-Encoded lncRNA MALAT1 Epigenetically Controls Metabolic Reprogramming in HCC Cells through the Mitophagy Pathway

Phenome-wide and expression quantitative trait locus associations of coronavirus disease 2019 genetic risk loci

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