PUBLICATION

Zebrafish Melanoma-Derived Interstitial EVs Are Carriers of ncRNAs That Induce Inflammation

Authors
Biagini, V., Busi, F., Anelli, V., Kerschbamer, E., Baghini, M., Gurrieri, E., Notarangelo, M., Pesce, I., van Niel, G., D'Agostino, V.G., Mione, M.
ID
ZDB-PUB-220530-14
Date
2022
Source
International Journal of Molecular Sciences   23(10): (Journal)
Registered Authors
Anelli, Viviana, Mione, Marina
Keywords
P and MRP RNAse, danio rerio, exosomes/extracellular vesicles, long ncRNA, melanoma
Datasets
GEO:GSE189352
MeSH Terms
  • Animals
  • Extracellular Vesicles*/metabolism
  • Inflammation/genetics
  • Inflammation/metabolism
  • Melanoma*/genetics
  • Melanoma*/metabolism
  • RNA, Untranslated/metabolism
  • Zebrafish/genetics
(all 8)
PubMed
35628321 Full text @ Int. J. Mol. Sci.
Abstract
Extracellular vesicles (EVs) are membranous particles released by all cell types. Their role as functional carrier of bioactive molecules is boosted by cells that actively secrete them in biological fluids or in the intercellular space (interstitial EVs, iEVs). Here we have optimised a method for the isolation and characterization of zebrafish iEVs from whole melanoma tissues. Zebrafish melanoma iEVs are around 140 nm in diameter, as determined by nanoparticle tracking and transmission electron microscopy (TEM) analysis. Western blot analysis shows enrichment for CD63 and Alix in the iEV fraction, but not in melanoma cell lysates. Super resolution and confocal microscopy reveal that purified zebrafish iEVs are green fluorescent protein positive (GFP+), indicating that they integrate the oncogene GFP-HRASV12G used to induce melanoma in this model within their vesicular membrane or luminal content. Analysis of RNA-Seq data found 118 non-coding (nc)RNAs differentially distributed between zebrafish melanoma and their iEVs, with only 17 of them being selectively enriched in iEVs. Among these, the RNA components of RNAses P and MRP, which process ribosomal RNA precursors, mitochondrial RNAs, and some mRNAs, were enriched in zebrafish and human melanoma EVs, but not in iEVs extracted from brain tumours. We found that melanoma iEVs induce an inflammatory response when injected in larvae, with increased expression of interferon responsive genes, and this effect is reproduced by MRP- or P-RNAs injected into circulation. This suggests that zebrafish melanoma iEVs are a source of MRP- and P-RNAs that can trigger inflammation in cells of the innate immune system.
Genes / Markers
Marker Marker Type Name
canxGENEcalnexin
ifit10GENEinterferon-induced protein with tetratricopeptide repeats 10
isg15GENEISG15 ubiquitin like modifier
oip5-as1LINCRNAGoip5 antisense RNA 1
pdcd6ipGENEprogrammed cell death 6 interacting protein
rmrpNCRNAGRNA component of mitochondrial RNA processing endoribonuclease
rnu6-1NCRNAGRNA, U6 small nuclear 1
rpph1GENEribonuclease P RNA component H1
snord30SNORNAGsmall nucleolar RNA, C/D box 30
1 - 9 of 9
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Figures
Figure Gallery (6 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
canxhzm5Et; io006Tgstandard conditionsAdultNot DetectedWB
canxhzm5Et; io006Tgstandard conditionsAdultWB
pdcd6iphzm5Et; io006Tgstandard conditionsAdultWB
pdcd6iphzm5Et; io006Tgstandard conditionsAdultNot DetectedWB
1 - 4 of 4
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Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl22TgTransgenic Insertion
    hzm1EtTransgenic Insertion
      hzm5EtTransgenic Insertion
        i113TgTransgenic Insertion
          io006TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            Human Disease Fish Conditions Evidence
            melanomahzm5Et; io006Tgstandard conditionsTAS
            1 - 1 of 1
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            Sequence Targeting Reagents
            No data available
            Fish
            Fish
            hzm5Et; io006Tg
            1 - 1 of 1
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            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            GAL4TA4EFGGAL4TA4
            GFPEFGGFP
            mCherryEFGmCherry
            1 - 4 of 4
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            Mapping
            No data available
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            Citation
            Biagini, V., Busi, F., Anelli, V., Kerschbamer, E., Baghini, M., Gurrieri, E., Notarangelo, M., Pesce, I., van Niel, G., D'Agostino, V.G., Mione, M. (2022) Zebrafish Melanoma-Derived Interstitial EVs Are Carriers of ncRNAs That Induce Inflammation. International Journal of Molecular Sciences. 23(10).