Epigenomic Hard Drive Imprinting: A Hidden Code Beyond the Biological Death of Cancer Patients

Pritish Nilendu, Nilesh Kumar Sharma, Pritish Nilendu, Nilesh Kumar Sharma

Abstract

Several genetic and epigenetic theories have been suggested to explain the intricacies of life and death. However, several questions remain unsettled regarding cellular death events, particularly of living tissue in the case of cancer patients, such as the fate and adaptation of cancer cells after biological death. It is possible that cancer cells can display the intent to communicate with the external environment after biological death by means of molecular, genetic, and epigenetic pathways. Whether these cancer cells contain special information in the form of coding that may help them survive beyond the biological death of cancer patients is unknown. To understand these queries in the cancer field, we hypothesize the epigenomic hard drive (EHD) as a cellular component to record and store global epigenetic events in cancerous and non-cancerous tissues of cancer patients. This mini-review presents the novel concept of EHD that is reinforced with the existing knowledge of genetic and epigenetic events in cancer. Further, we summarize the EHD understanding that may impart much potential and interest for basic and clinical scientists to unravel mechanisms of carcinogenesis, therapeutic markers, and differential drug responses.

Keywords: Chromatin; Death; Environment; Epigenomics; Neoplasms.

Conflict of interest statement

CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1
The schematic representation of epigenomic hard drive (EHD) in tumor and normal tissue. This model takes into account of tumor microenvironment and macroenvironment contribution in shaping of EHD in tumor tissue.
Figure 2
Figure 2
Epigenomic hard drive (EHD) during chromatin alterations. (A) Diagram describes that a methyl and a phosphate group approach, causing addition of these groups respectively to chromatin. As this change is reversible methyl and phosphate groups get detached from chromatin. (B) This model depicts that SATB1 molecules bind to DNA sequence and cause chromatin remodelling with loop like formation of DNA, analogous to noodles, like shape of DNA for ease of transcription.
Figure 3
Figure 3
The analogous shape modelling/remodelling between spring and chromatin structure. Here with sequential twist and untwist of spring, texture and appearance may change, despite normal shape. Hence, there should be some recorder to monitor about the how many times this spring has gone through twist and untwist. We hypothesize that this spring model may be analogous to chromatin modelling in a cyclic and sequential manner involving writer, reader and eraser to achieve differential state of chromatin and gene expression in response to external clues. To record or store the data related to these sequential chromatin modeling, we suggest about the existence of additional mechanisms recording with a set of players able to record these chromatin alterations events.

References

    1. Pattabiraman DR, Weinberg RA. Tackling the cancer stem cells: what challenges do they pose? Nat Rev Drug Discov 2014;13: 497–512.10.1038/nrd4253
    1. Fuchs Y, Steller H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol 2015;16:329–44.10.1038/nrm3999
    1. Feinberg AP, Koldobskiy MA, Göndör A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet 2016;17:284–99.10.1038/nrg.2016.13
    1. Moran S, Martínez-Cardús A, Sayols S, Musulén E, Balañá C, Estival-Gonzalez A, et al. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol 2016;17:1386–95.10.1016/S1470-2045(16)30297-2
    1. Torres CM, Biran A, Burney MJ, Patel H, Henser-Brownhill T, Cohen AS, et al. The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity. Science 2016;353: aaf1644.10.1126/science.aaf1644
    1. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007;128: 683–92.10.1016/j.cell.2007.01.029
    1. Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet 2016;17:487–500.10.1038/nrg.2016.59
    1. Van Tongelen A, Loriot A, De Smet C. Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. Cancer Lett 2017;396:130–7.10.1016/j.canlet.2017.03.029
    1. Erlich Y, Zielinski D. DNA Fountain enables a robust and efficient storage architecture. Science 2017;355:950–4.10.1126/science.aaj2038
    1. De Silva PY, Ganegoda GU. New trends of digital data storage in DNA. Biomed Res Int 2016;2016:8072463.10.1155/2016/8072463
    1. Geiman TM, Robertson KD. Chromatin remodeling, histone modifications, and DNA methylation-how does it all fit together? J Cell Biochem 2002;87:117–25.10.1002/jcb.10286
    1. Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T. SATB1 targets chromatin remodelling to regulate genes over long distances. Nature 2002;419:641–5.10.1038/nature01084
    1. Cai S, Lee CC, Kohwi-Shigematsu T. SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Nat Genet 2006;38:1278–88.10.1038/ng1913
    1. Lee JJ, Kim M, Kim HP. Epigenetic regulation of long noncoding RNA UCA1 by SATB1 in breast cancer. BMB Rep 2016;49:578–83.10.5483/BMBRep.2016.49.10.156
    1. Hamm CA, Stevens JW, Xie H, Vanin EF, Morcuende JA, Abdulkawy H, et al. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors. BMC Cancer 2010;10:471.10.1186/1471-2407-10-471
    1. Manderwad GP, Gokul G, Kannabiran C, Honavar SG, Khosla S, Vemuganti GK. Hypomethylation of the DNMT3L promoter in ocular surface squamous neoplasia. Arch Pathol Lab Med 2010; 134:1193–6.
    1. Subramanyam D, Belair CD, Barry-Holson KQ, Lin H, Kogan SC, Passegué E, et al. PML-RAR{alpha} and Dnmt3a1 cooperate in vivo to promote acute promyelocytic leukemia. Cancer Res 2010;70:8792–801.10.1158/0008-5472.CAN-08-4481
    1. Richly H, Aloia L, Di Croce L. Roles of the Polycomb group proteins in stem cells and cancer. Cell Death Dis 2011;2:e204.10.1038/cddis.2011.84
    1. Sparmann A, van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 2006;6:846–56.10.1038/nrc1991
    1. Keibler MA, Wasylenko TM, Kelleher JK, Iliopoulos O, Vander Heiden MG, Stephanopoulos G. Metabolic requirements for cancer cell proliferation. Cancer Metab 2016;4:16.10.1186/s40170-016-0156-6
    1. Stein RA. Epigenetics and environmental exposures. J Epidemiol Community Health 2012;66:8–13.10.1136/jech.2010.130690
    1. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 2012;13:97–109.
    1. Hou L, Zhang X, Wang D, Baccarelli A. Environmental chemical exposures and human epigenetics. Int J Epidemiol 2012;41: 79–105.10.1093/ije/dyr154
    1. Toraño EG, García MG, Fernández-Morera JL, Niño-García P, Fernández AF. The impact of external factors on the epigenome: in utero and over lifetime. Biomed Res Int 2016;2016:2568635.10.1155/2016/2568635
    1. Romani M, Pistillo MP, Banelli B. Environmental epigenetics: crossroad between public health, lifestyle, and cancer prevention. Biomed Res Int 2015;2015:587983.10.1155/2015/587983
    1. Herceg Z. Epigenetic mechanisms as an interface between the environment and genome. Adv Exp Med Biol 2016;903:3–15.10.1007/978-1-4899-7678-9_1
    1. Zannas AS, Chrousos GP. Epigenetic programming by stress and glucocorticoids along the human lifespan. Mol Psychiatry 2017; 22:640–46.10.1038/mp.2017.35
    1. Ratovitski EA. Anticancer natural compounds as epigenetic modulators of gene expression. Curr Genomics 2017;18:175–205.10.2174/1389202917666160803165229
    1. Hahn O, Grönke S, Stubbs TM, Ficz G, Hendrich O, Krueger F, et al. Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism. Genome Biol 2017;18:56.10.1186/s13059-017-1187-1
    1. Xu X, Farach-Carson MC, Jia X. Three-dimensional in vitro tumor models for cancer research and drug evaluation. Biotechnol Adv 2014;32:1256–68.10.1016/j.biotechadv.2014.07.009
    1. Yamada KM, Cukierman E. Modeling tissue morphogenesis and cancer in 3D. Cell 2007;130:601–10.10.1016/j.cell.2007.08.006
    1. Hoffman RM. Live cell imaging in live animals with fluorescent proteins. Methods Enzymol 2012;506:197–224.10.1016/B978-0-12-391856-7.00035-4

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever