The cell survival pathways of the primordial RNA-DNA complex remain conserved in the extant genomes and may function as proto-oncogenes

Sinkovics, Joseph G.

doi:10.1556/eujmi-d-14-00034

Cited by 10 publications

(13 citation statements)

References 147 publications

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“…Collectively, exosomes may present with a heterogeneous mixture of all cellular componenets ( Fig. 1), raising an intriguing notion that exosomes may resemble "primordial"-like vesicles (Sinkovics 2015;Kalluri 2016). The evidence for the functional impact of cellular exchange of exosomal content, such as signaling molecules, messenger RNA (mRNA), and microRNA (miRNA), implicates exosomes in widespread multiorgan communication.…”

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confidence: 99%

Discovery of Double-Stranded Genomic DNA in Circulating Exosomes

Kalluri

LeBleu

2016

Cold Spring Harb Symp Quant Biol

154

108

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It is becoming increasingly clear that small vesicles released from cells (extracellular vesicles [EVs]) represent a heterogeneous population implicated in cell-to-cell communication. The classifications and nomenclature of EVs are evolving as enrichment strategies and specific characteristics are being unraveled. At present, physical properties of EVs-namely, size, shape, and density-are often used to identify subpopulations of EVs. A distinct group of EVs, termed exosomes, largely defined by their small size (∼40-150 nm) and proposed subcellular origin, has been extensively studied in several aspects of cancer biology. Exosomes are implicated in modulating behavior of cancer cells as well as the immune and angiogenic responses in tumors, possibly contributing to cancer progression locally and systemically. Most intriguingly, the nucleic acid content of exosomes has been proposed to play a role in oncogenic transformation and transfer of cancer-specific genome to promote cancer pathogenesis. Here, we specifically focus on the discovery of exosomal DNA, studies related to the origin of genomic DNA in exosomes, and its utility in cancer diagnosis and disease monitoring.

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confidence: 99%

Discovery of Double-Stranded Genomic DNA in Circulating Exosomes

Kalluri

LeBleu

2016

Cold Spring Harb Symp Quant Biol

154

108

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“…RGV regions homologous to the v-myb oncogene are also found in both halophilic and methanophilic archaebacteria 25 . The set of serinethreonine protein kinases, listed in our functional annotations, are very similar to the eukaryotic ones, but simultaneously homologous to those identified in some archaebacteria including Methanococcus vannielii, M. voltae and M. Thermolitotrophicus [26][27][28] .The predicted RGV helicase is an archaebacterial protein involved in the tumour-suppressor pathways 29 . In addition, cyclin dependent kinases (CDKs) and cells division proteins, playing an essential role in the common archeal cell cycle, have been predicted to be part of this of RGV genome 30 .…”

Section: Discussionmentioning

confidence: 61%

Discovery of the First Human Retro-Giant Virus: Description of its morphology, retroviral kinase and ability to induce tumours in mice

Lusi

Caicci

2019

Preprint

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BackgroundThe study of retroviruses dates back to the early 1900s during investigations on neoplastic diseases in chickens. Subsequently, Robert Gallo reported the first human retrovirus HLTV in 1980. What we report here is not an archetypal retrovirus, but the discovery of an oncogenic giant microbial agent with a mega-genome, where the transforming retroviral nature co-exists with multiple archaeal oncogenes.MethodsAfter their isolation from human T cells Leukaemia, these organisms were examined at electron microscopy, tested for reverse transcriptase activity, fully sequenced, used for transformation tests on NIH-3T3 cells in vitro and tumours formation in mice. Same type of particles were also isolated from Canine Transmissible Venereal Tumour (CTVT), the oldest contagious cancer in nature.ResultsEM showed the presence of giant viral particles displaying retroviral antigens. These microbial entities harbour in their mega-genome a transforming retroviral kinase, cell-based oncogenes and have reverse transcriptase activity. The purified viral particles transformed NIH-3T3 cells and induced metastatic tumours in nude mice, three weeks post infection. Ruling out the possible presence of filterable retroviruses, a filtered supernatant did not display RT activity and did not transforms.ConclusionsWe discovered an ancestral microbial agent, acutely transforming. For its giant dimensions, the ability to retain the Gram stain, the presence of a mega-genome and its retroviral nature, we tentatively named the agent Retro-Giant-Virus (RGV). However, distinct from amoeba giant Mimiviruses, this transforming human agent has a different nature and does not require for its isolation amoeba co-culture, since amoeba is not its natural host.The morphology, biology and genetic features allocate this mammalian giant microbe halfway in between a classic oncogenic virus and an infectious cancer cell. Its transforming nature goes with its constant ability to induce tumours formation in mice.

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“…Unicellular eukaryotes do not operate the Wnt pathway. The Wnt pathway (wingless; Drosophila ; integrated, mouse) in the ontogenesis of Ciona intestinalis was recently reviewed ( 125 ). Cnidarians and ctenophores in their ontogenesis utilize the Wnt pathway.…”

Section: The Primordial Cell Survival Pathways Become Proto-oncogementioning

confidence: 99%

The cnidarian origin of the proto-oncogenes NF-κB/STAT and WNT-like oncogenic pathway drives the ctenophores (Review)

Sinkovics

2015

Int J Oncol

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The cell survival pathways of the diploblastic early multicellular eukaryotic hosts contain and operate the molecular machinery resembling those of malignantly transformed individual cells of highly advanced multicellular hosts (including Homo). In the present review, the STAT/NF-κB pathway of the cnidarian Nematostella vectensis is compared with that of human tumors (malignant lymphomas, including Reed-Sternberg cells) pointing out similarities, including possible viral initiation in both cases. In the ctenophore genome and proteome, β-catenin gains intranuclear advantages due to a physiologically weak destructive complex in the cytoplasm, and lack of natural inhibitors (the Dickkopfs). Thus, a scenario similar to what tumor cells initiate and achieve is presented through several constitutive loss-of-function type mutations in the destructive complex and in the elimination of inhibitors. Vice versa, malignantly transformed individual cells of advanced multicellular hosts assume pheno-genotypic resemblance to cells of unicellular or early multicellular hosts, and presumably to their ancient predecessors, by returning to the semblance of immortality and to the resumption of the state of high degree of resistance to physicochemical insults. Human leukemogenic and oncogenic pathways are presented for comparisons. The supreme bioengineers RNA/DNA complex encoded both the malignantly transformed immortal cell and the human cerebral cortex. The former generates molecules for the immortality of cellular life in the Universe. The latter invents the inhibitors of the process in order to gain control over it.

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The cell survival pathways of the primordial RNA-DNA complex remain conserved in the extant genomes and may function as proto-oncogenes

Cited by 10 publications

References 147 publications

Discovery of Double-Stranded Genomic DNA in Circulating Exosomes

Discovery of Double-Stranded Genomic DNA in Circulating Exosomes

Discovery of the First Human Retro-Giant Virus: Description of its morphology, retroviral kinase and ability to induce tumours in mice

The cnidarian origin of the proto-oncogenes NF-κB/STAT and WNT-like oncogenic pathway drives the ctenophores (Review)

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