Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine

Vinogradov, Alexander E.; Anatskaya, Olga V.

doi:10.3390/ijms231911486

Cited by 3 publications

(6 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, there can be a synergism between the high gene expression in the UC center and the UC interactome attractor that is triggered by intensive cell stress, especially during cell proliferation. As a result, the Waddington epigenetic landscape of ontogenesis [ 70 , 71 ], which, in accordance with the biogenetic law, roughly recapitulates phylogenesis [ 57 , 72 ], can turn over. (The biogenetic law was validated on the cellular level [ 57 ].)…”

Section: Discussionmentioning

confidence: 99%

“…As a result, the Waddington epigenetic landscape of ontogenesis [ 70 , 71 ], which, in accordance with the biogenetic law, roughly recapitulates phylogenesis [ 57 , 72 ], can turn over. (The biogenetic law was validated on the cellular level [ 57 ].) In normal cells, this landscape is slanted towards cell differentiation, yet under stressful conditions it can be counteracted by the activity of UC attractor, causing landscape turnover and cell dedifferentiation ( Figure 11 ).…”

Section: Discussionmentioning

confidence: 99%

“…The extracellular matrix “normalization” can also be proposed as a potential strategy for anti-malignant treatment [ 104 ]. As for regenerative medicine, healthy regeneration could involve an ontogenetic reversal to a younger organism’s state (which, according to the biogenetic law, corresponds to earlier multicellular stages) without a phylogenetic reversal to a unicellular cell state [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…We assume that these random walks can simulate random alterations in the interactome caused by mutations in the encoding gene or disturbances in gene expression or protein configuration. It was shown previously that alterations in protein interactions are associated with changes in gene expression [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

“…The evolutionary stages at the top are visualized by recent representatives. (According to the biogenetic law, ontogenesis roughly recapitulates phylogenesis [ 57 , 72 ]).…”

Section: Figurementioning

confidence: 99%

See 4 more Smart Citations

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Vinogradov

Anatskaya

2023

IJMS

Self Cite

View full text Add to dashboard Cite

Using meta-analyses, we introduce a unicellular attractor (UCA) model integrating essential features of the ‘atavistic reversal’, ‘cancer attractor’, ‘somatic mutation’, ‘genome chaos’, and ‘tissue organization field’ theories. The ‘atavistic reversal’ theory is taken as a keystone. We propose a possible mechanism of this reversal, its refinement called ‘gradual atavism’, and evidence for the ‘serial atavism’ model. We showed the gradual core-to-periphery evolutionary growth of the human interactome resulting in the higher protein interaction density and global interactome centrality in the UC center. In addition, we revealed that UC genes are more actively expressed even in normal cells. The modeling of random walk along protein interaction trajectories demonstrated that random alterations in cellular networks, caused by genetic and epigenetic changes, can result in a further gradual activation of the UC center. These changes can be induced and accelerated by cellular stress that additionally activates UC genes (especially during cell proliferation), because the genes involved in cellular stress response and cell cycle are mostly of UC origin. The functional enrichment analysis showed that cancer cells demonstrate the hyperactivation of energetics and the suppression of multicellular genes involved in communication with the extracellular environment (especially immune surveillance). Collectively, these events can unleash selfish cell behavior aimed at survival at all means. All these changes are boosted by polyploidization. The UCA model may facilitate an understanding of oncogenesis and promote the development of therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The evolutionary stages at the top are visualized by recent representatives. (According to the biogenetic law, ontogenesis roughly recapitulates phylogenesis [ 57 , 72 ]).…”

Section: Figurementioning

confidence: 99%

See 3 more Smart Citations

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Vinogradov

Anatskaya

2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

Gradistics: An underappreciated dimension in evolutionary space

Vinogradov

Anatskaya

2023

Biosystems

View full text Add to dashboard Cite

Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

Anatskaya

Runov

Ponomartsev

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Many cardiovascular diseases originate from growth retardation, inflammation, and malnutrition during early postnatal development. The nature of this phenomenon is not completely understood. Here we aimed to verify the hypothesis that systemic inflammation triggered by neonatal lactose intolerance (NLI) may exert long-term pathologic effects on cardiac developmental programs and cardiomyocyte transcriptome regulation. Using the rat model of NLI triggered by lactase overloading with lactose and the methods of cytophotometry, image analysis, and mRNA-seq, we evaluated cardiomyocyte ploidy, signs of DNA damage, and NLI-associated long-term transcriptomic changes of genes and gene modules that differed qualitatively (i.e., were switched on or switched off) in the experiment vs. the control. Our data indicated that NLI triggers the long-term animal growth retardation, cardiomyocyte hyperpolyploidy, and extensive transcriptomic rearrangements. Many of these rearrangements are known as manifestations of heart pathologies, including DNA and telomere instability, inflammation, fibrosis, and reactivation of fetal gene program. Moreover, bioinformatic analysis identified possible causes of these pathologic traits, including the impaired signaling via thyroid hormone, calcium, and glutathione. We also found transcriptomic manifestations of increased cardiomyocyte polyploidy, such as the induction of gene modules related to open chromatin, e.g., “negative regulation of chromosome organization”, “transcription” and “ribosome biogenesis”. These findings suggest that ploidy-related epigenetic alterations acquired in the neonatal period permanently rewire gene regulatory networks and alter cardiomyocyte transcriptome. Here we provided first evidence indicating that NLI can be an important trigger of developmental programming of adult cardiovascular disease. The obtained results can help to develop preventive strategies for reducing the NLI-associated adverse effects of inflammation on the developing cardiovascular system.

show abstract

Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine

Cited by 3 publications

References 63 publications

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

Gradistics: An underappreciated dimension in evolutionary space

Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

Contact Info

Product

Resources

About