Epigenetic Modification in Human Thyroid Cancer - Essay Example

Epigenetics Every cell in the human body has the same genetic material however, not each and every one ofthem behaves in the same pattern owing to genetic regulations. The term “epigenetics”, refers to the regulatory mechanism which has the ability switch “on” and switch “off” genes and thereby contribute to alteration of the genetic expressions. Epigenetic alterations influence the interactions of the DNA and do not include direct changes in the DNA sequence itself (Williams, 2013). Previously it was just defined as the study of non-sequence changes of bases such as DNA methylation which can be inherited as well (Feinberg and Irizarry, 2009). Neo-Darwinism, has been stretched to incorporate epigenetics from an evolutionary perspective and even from a Non-Lamarckian viewpoint, epigenetics does have an important role in evolution. Epigenetic changes are heritable in nature and in some cases large unexplained heritance of certain characters does take place yet this is important to maintain both genotypic and phenotypic variability (Feinberg and Irizarry, 2009). Epigenetic modifications are extremely crucial to maintain human body functions and improper functioning of these modifications can cause adverse health effects and lead to major diseases of the human body. Epigenetic Regulation and Trangenerational Effects There are several epigenetic processes that have been identified such as DNA methylation, acetylation,sumolyation, ubiquitinization, phosphorylation and chromatin alteration. Epigenetic events include modifications of the histone proteins and leads to regulation of chromatin structure and subsequently lead to alteration of the gene function. Researchers have identified deficiency of biotin as one of the major regulatory factors in modifying the chromatin structure. In fact, epigenetics involves the transgenerational transmittance of phenotypic characters which previously solely attributed to genetics. Transgeneration epigenetics refers to the inheritance of information from one organism to another. The transfer of certain characters for example maternal care have been studied. According to a study conducted by Champagne in 2008, epigenetic alterations helps in transferring of traits such as maternal care form the mother to the female off-spring, post-partum (Champagne, 2008). Such transfers have mostly been attributed to epigenetics change sin neuronal and endocrine processes on the body. Epigenetic Mechanisms Epigenetics has its affects on the different processes of the human body and on the overall health of a person as well. Ranging from normal development , neurobiology and metabolism to influencing grave diseases such as Alzheimer’s and cancer development, epigenetics has the capability to control most processes and hence has increasingly emerged as one of the most researched upon topics in the recent times. Epigenetics and Development Increasing number of evidences have already established that epigenetics like genetics also plays an important role during development. It is not only the epigenetic modifications such as methylation or alterations in histone structure that modifies gene expression but long-distance chromosomal interactions also have capability to do the same (Kiefer, 2007). Important developmental events such as X chromosome inactivation, genomic imprinting, patterning by Hox genes and even neuronal development is controlled by epigenetic modifications. Epigenetics and Cancer Cancer, to this day remains one of the main focus of research. Most of the molecular and the genetic aspects of cancer are known. However, since epigenetic modification are extremely essential for proper maintenance of the main body functions and gene expressions. In fact, disruption of proper regulation of epigenetic processes can affect these genetic expressions and lead to alterations in gene functioning and lead to cancer (Sharma et al, 2010). Thyroid carcinoma is one of the most common endocrine malignancy and over 95% of the thyroid carcinomas occurs in the follicular cells. Studies have established the epigenetic regulations such as DNA methylation in the CpG regions in the micro RNAs modifies its expression and leads to profiles that can be linked to cancer (Faam et al, 2015). Aberrant methylation of the DNA of certain proto-oncogenes and tumour suppressor genes has been studied in human thyroid cancers. Tumour suppressor genes which can be epigenetically regulated include PTEN, RASSF1A, TIMP3, SLC5A8, DAPK and RAP1GAP. Influence of Epigenetics on Neurobiology The association of the neurobiology of humans and epigenetic regulation is a complex one. It has long been known that interaction between the gene and the environment has an impact on the development and functioning of the central nervous system. Alzheimer’s which a grave age-related disorder primarily caused by development of plaques and accumulation of neurofibrillary tangles and results in degeneration of the nerve fibres of the brain causing debilitating symptoms has also been associated to epigenetic regulation. Study conducted in mice models have shown evidence of chromatin alterations in Alzheimer’s. A coordinated down-regulation of certain genes such as synaptic plasticity gene and up regulation of certain immune response gene have been noticed in mice afflicted with Alzheimer-like disease (Gjoneska et al, 2015). Epigenetic regulation also has the ability to induce differential response to different stress levels. Stress is a common factor that is very much prevalent in every one’s lives today. Stress along with the corticosteroid hormones of the body has the ability to modify the functioning of the brain and plasticity (Hunter, 2012). However, genetics alone is not sufficient to shed light on the long-time affect of stress on brain and behaviour and this is where epigenetic come in since it has the ability to deepen our level of understanding of the association of stress and brain functioning. Research has shown that the epigenome and the stress axis, though not thoroughly studied as of yet, that stress has the ability to change the brain’s functioning and structure. Epigenetic regulation does not only modify an individual’s response to stress but also affects the mood. Antimanic effect of valproate, which is a histone deacetylase inhibitor and a methyl group donor in FDNA methylation of epigenetic regulation has been associated with DNA methylation in individual’s with mood disorders (McGowan and Kato, 2007). Hypomethylation of the gene PPIEL was found to be present in bipolar disease indicating link between the epigenome and mood. Epigenetics and gut biota It is already known that epigenetic modifications play a very important role on influencing the brain and a person’s behaviour pattern. Another important fact that arises from host-interaction studies is that the gut biota composition also affects a person’s behaviour and cognition. The microbiota-gut-rain axis is the name given to the relation between the body’s microbial flora and the subsequent effect on the brain and behaviour. There are several ways in which the gut flora can influence the brain- the product of gut-microbes can affect brain plasticity which influences neuronal transcription and subsequently affects the behaviour of the individual. It is possible that the microbiota itself acts as epigenetic entity and lead to direct epigenetic modification (Stillling et al, 2014). Affect of Epigenetics on metabolism Metabolism problems such as development of obesity especially among children regardless of the health status of their mothers, does not necessarily mean that it has been genetically inherited but may also depend on the genetic expression. In fact, the fact that normal children can be born to obese mothers or an obese child may be born to a normal mother supports the fact that things beyond genetics may play a pivotal role in controlling the onset of obesity. Whether the child is born obese or not primarily depends on the uterine environment, maternal glucose and exposure to lipid levels while inside the maternal body ( Heerwagen et al, 2010). The exposure to lipid again depends on the maternal intake of high fatty diet which controls the level of fat in the body and also the level of lipid that foetus is exposed to. Similar epigenetic controlling can be seen in another major metabolic disorder- Diabetes type II. In fact, it has been seen that foetal programming and epigenetic mechanisms are responsible for development of diabetes. Most, importantly the fact that development of such metabolic problems can be traced back to foetal programming, makes prevention and even cure much more possible. Research has shown that inadequate beta cells and adipose tissue responses to long-time fuel excesses also causes diabetes onset by causing nutrient spillover, insulin resistance and metabolic stress (Nolan et al, 2011). Chronic stress on metabolism processes can cause irreversible damage on the organs as well. Epigenetic regulation also regulates insulin resistance in the uterus which implies that treatment options may be explored even before a child is born. Immunity and Epigenetics The immune system helps the body to fight against invasion of pathogens and thereby safeguards the body. Most of the person’s ability to fight is innate in nature and hence the immunity of a person is already coded in the germ line characters that have been inherited. It has been seen that inflammation, which is a result of an immune response, regardless of it being acute or chronic is known to have a intimate association with epigenetics (McCall et all, 2010). Serious immune responses and all of the four stages of inflammatory response of the body i.e. homeostasis, incitement, evolution and resolution can also be controlled by regulation of the epigenome. Conclusion It is a fact that the study of epigenetics can clearly explain things that previously was not explainable using genetics alone. Epigenetic modifications controls each and every mechanism in the body. It is responsible for both good and bad health. Several diseases such as diabetes, endocrine diseases and even cancer may have epigenetic origin. One of the most astonishing findings related to epigenetics is its ability to affect psychological processes as well especially those controlled by neurobiological aspects. We have already seen how epigenetic alterations not only raises risk of cancer but also influences several other body processes as well. However, a thorough understanding of such alterations can also help in designing therapeutic approaches as well. REFERENCES Champagne,FA. Epigenetic Mechanisms and the Transgenerational Effects of Maternal Care. Front Neuroendocrinol. 2008; 29(3):386-397. Faam,B et al. Epigenetic modifications in human thyroid cancer. Biomedical Reports.2015; 3 (1):3-8. Feinberg AP, Irizarry RA. Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease. Proceedings of the National Academy of Sciences of the United States of America. Jan 26 2010;107:1757-1764. Gjoneska, E., Pfenning, A. R., Mathys, H., Quon, G., Kundaje, A., Tsai, L. H., & Kellis, M. (2015). Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer/"s disease. Nature, 518(7539), 365-369. Heerwagen MJR, Miller MR, Barbour LA, Friedman JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am. J. Physiol.-Regul. Integr. Comp. Physiol. Sep 2010;299(3):R711-R722. Hunter RG. Epigenetic effects of stress and corticosteroids in the brain. Frontiers in Cellular Neuroscience. Apr 19 2012. Kiefer,JC. Epigenetics in Development. Developmental Dynamics.2007; 236(4): 1144-1156. McCall CE, Yoza B, Liu T, El Gazzar M. Gene-Specific Epigenetic Regulation in Serious Infections with Systemic Inflammation. Journal of Innate Immunity. 2010;2(5):395-405. McGowan,P.O and Kato,T. Epigenetics and Mood Disorders. Environmental Health and Preventive Medicine. 2008;13 (1):16-24. Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. Jul 9 2011. Sharma,S, Kelly,T and Jones, P.A. Epigenetics in cancer.Carcionogenesis.2010; 31(3):27-36. Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour -epigenetic regulation of the gut-brain axis. Genes Brain and Behavior. Jan 2014;13(1):69-86. William, S.C.Epigenetics. Proceedings o f the National Academy of Sciences of the United States of America.2013; 110 (9): p.3209-3213. Read More