{"id":757,"date":"2023-04-03T07:46:01","date_gmt":"2023-04-03T07:46:01","guid":{"rendered":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/?post_type=chapter&#038;p=757"},"modified":"2023-04-07T10:45:05","modified_gmt":"2023-04-07T10:45:05","slug":"chapter-5-mis-regulated-gene-expression-in-disease","status":"publish","type":"chapter","link":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/chapter\/chapter-5-mis-regulated-gene-expression-in-disease\/","title":{"raw":"Chapter 5: Mis regulated Gene expression in disease","rendered":"Chapter 5: Mis regulated Gene expression in disease"},"content":{"raw":"<div class=\"textbox textbox--learning-objectives\"><header class=\"textbox__header\">\r\n<p class=\"textbox__title\">Learning Objectives<\/p>\r\n\r\n<\/header>\r\n<div class=\"textbox__content\">\r\n\r\n<span>By the end of this chapter, readers will be able to:<\/span>\r\n<ul>\r\n \t<li><span style=\"font-size: 1em\">Discuss the importance of gene expression regulation<\/span><\/li>\r\n \t<li>Explain the link between dysregulated gene expression and cancer<\/li>\r\n \t<li>Discuss the role of dysregulated gene expression in auto immune diseases<\/li>\r\n<\/ul>\r\n<\/div>\r\n<\/div>\r\n<h2 class=\"editable\" style=\"text-align: center\">\u00a0Altered Gene Expression and Cancer<\/h2>\r\nAltered gene expression or dysregulated gene expression plays a role in the development of disease like Cancer. Proteins are turned on or expressed by gene activation and are turned off by gene silencing. This gene expression regulation determines the overall activity of the cell. A gene that is not normally expressed in a cell can be switched on and expressed at high levels due to\u00a0 gene mutation or changes in gene regulation ( epigenetic, transcription, post-transcription, translation, or post-translation).Changes at each of these levels can be detected in different types of cancer\u00a0 in different individuals. Scientific\u00a0 studies had reported changes in histone acetylation , activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification etc.,\u00a0 to be involved in the development of various cancers.\r\n\r\n<strong>[pb_glossary id=\"952\"]Tumor suppressor genes[\/pb_glossary]<\/strong>\r\n\r\nThese are genes active in normal cells that function to prevent uncontrolled cellular proliferations example, p53 gene .This gene is <span>\u00a0mutated in over 50 percent of all cancer types. The p53 protein itself functions as a transcription factor and can bind to promoters of genes to initiate transcription. Therefore, the mutation of p53 in cancer\u00a0 alter the transcriptional activity of its target genes.<\/span>\r\n\r\n<strong>Proto-Oncogenes\u00a0<\/strong>\r\n\r\n<span>[pb_glossary id=\"954\"]Proto-oncogenes [\/pb_glossary]which are positive cell-cycle regulators. When mutated, proto-oncogenes can become oncogenes and cause cancer..<\/span>\r\n\r\n<span>When their expression is deregulated in cancers\u00a0 there can be overexpression and can become the oncogene\u00a0 leading to uncontrolled cell growth. For example the Myc protein ,which is a transcription factor .Aberrantly activated\u00a0 Myc results in\u00a0 a cancer of the lymph system called <strong>[pb_glossary id=\"956\"]Burkett\u2019s Lymphoma.[\/pb_glossary]<\/strong> Overexpression of myc transforms normal B cells into cancerous cells that continue to grow uncontrollably and develop as tumors of the\u00a0 jaw or\u00a0 mouth that interfere with the ability to eat.<\/span>\r\n\r\n<strong>Epigenetic Alterations<\/strong>\r\n<p id=\"fs-id1675964\">Silencing genes through epigenetic mechanisms is also very common in cancer cells. Certain histone and DNA\u00a0 modifications are associated with silenced genes. The DNA in the promoter region of silenced genes is methylated on cytosine DNA residues in CpG islands in most cancer cells.<\/p>\r\n<strong>Altered Transcription control<\/strong>\r\n\r\n<span>\u00a0Mutations may activate transcription factors and can increase the binding of a transcription factor to\u00a0 a promoter. This could lead to increased transcriptional activation of that gene. This in turn\u00a0 results in modified cell growth and proliferation. Also mutations in promoter or enhancer region can increase the binding ability of a transcription factor. This could also lead to the increased transcription and aberrant gene expression that is seen in cancer cells. For example Breast cancer cells over express<strong> the epidermal growth factor receptor (EGFR).\u00a0<\/strong><\/span><span>The EGFR pathway activates many protein kinases that, in turn, activate many transcription factors that control genes involved in cell growth. Therefore\u00a0 drugs that prevent the activation of EGFR have been developed\u00a0 to treat breast cancer .<\/span>\r\n\r\n<strong>Altered expression of miRNAs<\/strong>\r\n\r\n<span>miRNAs bind to the 3\u2032 UTR of RNA molecules and degrade them.\u00a0 Overexpression of these miRNAs could be detrimental to normal cellular activity. Increased expression of\u00a0 miRNAs could\u00a0 decrease the RNA population and\u00a0 in\u00a0 turn decrease protein expression. Several studies have demonstrated\u00a0 change in the miRNA population in specific cancer types. Aberrantly expressed miRNAs is also reported contributing to the pathogenesis of multiple sclerosis\u00a0<\/span>\r\n\r\n<strong>Altered Post translational control<\/strong>\r\n\r\nIncreased translation of a protein, changes in protein phosphorylation , variants of alternative splicing are found in cancer cells. For example ,the c-Flip protein ,\u00a0 <span>a protein involved in mediating the cell death pathway, exists in two forms: long (c-FLIPL) and short (c-FLIPS). In normal cells b<span style=\"text-align: initial;font-size: 1em\">oth the isoforms\u00a0 \u00a0 \u00a0 \u00a0 appear to be involved in initiating controlled cell death mechanisms . However, in colon cancer cells,\u00a0 long form\u00a0 is seen to over expressed . This results in\u00a0 increased cell growth instead of cell death.\u00a0<\/span><\/span>\r\n\r\n&nbsp;","rendered":"<div class=\"textbox textbox--learning-objectives\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\">Learning Objectives<\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p><span>By the end of this chapter, readers will be able to:<\/span><\/p>\n<ul>\n<li><span style=\"font-size: 1em\">Discuss the importance of gene expression regulation<\/span><\/li>\n<li>Explain the link between dysregulated gene expression and cancer<\/li>\n<li>Discuss the role of dysregulated gene expression in auto immune diseases<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<h2 class=\"editable\" style=\"text-align: center\">\u00a0Altered Gene Expression and Cancer<\/h2>\n<p>Altered gene expression or dysregulated gene expression plays a role in the development of disease like Cancer. Proteins are turned on or expressed by gene activation and are turned off by gene silencing. This gene expression regulation determines the overall activity of the cell. A gene that is not normally expressed in a cell can be switched on and expressed at high levels due to\u00a0 gene mutation or changes in gene regulation ( epigenetic, transcription, post-transcription, translation, or post-translation).Changes at each of these levels can be detected in different types of cancer\u00a0 in different individuals. Scientific\u00a0 studies had reported changes in histone acetylation , activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification etc.,\u00a0 to be involved in the development of various cancers.<\/p>\n<p><strong><a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_757_952\">Tumor suppressor genes<\/a><\/strong><\/p>\n<p>These are genes active in normal cells that function to prevent uncontrolled cellular proliferations example, p53 gene .This gene is <span>\u00a0mutated in over 50 percent of all cancer types. The p53 protein itself functions as a transcription factor and can bind to promoters of genes to initiate transcription. Therefore, the mutation of p53 in cancer\u00a0 alter the transcriptional activity of its target genes.<\/span><\/p>\n<p><strong>Proto-Oncogenes\u00a0<\/strong><\/p>\n<p><span><a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_757_954\">Proto-oncogenes <\/a>which are positive cell-cycle regulators. When mutated, proto-oncogenes can become oncogenes and cause cancer..<\/span><\/p>\n<p><span>When their expression is deregulated in cancers\u00a0 there can be overexpression and can become the oncogene\u00a0 leading to uncontrolled cell growth. For example the Myc protein ,which is a transcription factor .Aberrantly activated\u00a0 Myc results in\u00a0 a cancer of the lymph system called <strong><a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_757_956\">Burkett\u2019s Lymphoma.<\/a><\/strong> Overexpression of myc transforms normal B cells into cancerous cells that continue to grow uncontrollably and develop as tumors of the\u00a0 jaw or\u00a0 mouth that interfere with the ability to eat.<\/span><\/p>\n<p><strong>Epigenetic Alterations<\/strong><\/p>\n<p id=\"fs-id1675964\">Silencing genes through epigenetic mechanisms is also very common in cancer cells. Certain histone and DNA\u00a0 modifications are associated with silenced genes. The DNA in the promoter region of silenced genes is methylated on cytosine DNA residues in CpG islands in most cancer cells.<\/p>\n<p><strong>Altered Transcription control<\/strong><\/p>\n<p><span>\u00a0Mutations may activate transcription factors and can increase the binding of a transcription factor to\u00a0 a promoter. This could lead to increased transcriptional activation of that gene. This in turn\u00a0 results in modified cell growth and proliferation. Also mutations in promoter or enhancer region can increase the binding ability of a transcription factor. This could also lead to the increased transcription and aberrant gene expression that is seen in cancer cells. For example Breast cancer cells over express<strong> the epidermal growth factor receptor (EGFR).\u00a0<\/strong><\/span><span>The EGFR pathway activates many protein kinases that, in turn, activate many transcription factors that control genes involved in cell growth. Therefore\u00a0 drugs that prevent the activation of EGFR have been developed\u00a0 to treat breast cancer .<\/span><\/p>\n<p><strong>Altered expression of miRNAs<\/strong><\/p>\n<p><span>miRNAs bind to the 3\u2032 UTR of RNA molecules and degrade them.\u00a0 Overexpression of these miRNAs could be detrimental to normal cellular activity. Increased expression of\u00a0 miRNAs could\u00a0 decrease the RNA population and\u00a0 in\u00a0 turn decrease protein expression. Several studies have demonstrated\u00a0 change in the miRNA population in specific cancer types. Aberrantly expressed miRNAs is also reported contributing to the pathogenesis of multiple sclerosis\u00a0<\/span><\/p>\n<p><strong>Altered Post translational control<\/strong><\/p>\n<p>Increased translation of a protein, changes in protein phosphorylation , variants of alternative splicing are found in cancer cells. For example ,the c-Flip protein ,\u00a0 <span>a protein involved in mediating the cell death pathway, exists in two forms: long (c-FLIPL) and short (c-FLIPS). In normal cells b<span style=\"text-align: initial;font-size: 1em\">oth the isoforms\u00a0 \u00a0 \u00a0 \u00a0 appear to be involved in initiating controlled cell death mechanisms . However, in colon cancer cells,\u00a0 long form\u00a0 is seen to over expressed . This results in\u00a0 increased cell growth instead of cell death.\u00a0<\/span><\/span><\/p>\n<p>&nbsp;<\/p>\n<div class=\"glossary\"><span class=\"screen-reader-text\" id=\"definition\">definition<\/span><template id=\"term_757_952\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_757_952\"><div tabindex=\"-1\"><p>Genes in normal cells that function to prevent uncontrolled cell divisions<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_757_954\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_757_954\"><div tabindex=\"-1\"><p>Genes when mutated that can become Oncogenes and cause cancer<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_757_956\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_757_956\"><div tabindex=\"-1\"><p>Cancer of the lymph system caused due to aberrant expression of Myc protein<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><\/div>","protected":false},"author":5,"menu_order":38,"template":"","meta":{"om_disable_all_campaigns":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_uf_show_specific_survey":0,"_uf_disable_surveys":false,"pb_show_title":"on","pb_short_title":"Mis regulated Gene expression in disease","pb_subtitle":"Mis regulated Gene expression in disease","pb_authors":["dr-v-malathi"],"pb_section_license":"cc-by-sa"},"chapter-type":[],"contributor":[61],"license":[54],"class_list":["post-757","chapter","type-chapter","status-publish","hentry","contributor-dr-v-malathi","license-cc-by-sa"],"aioseo_notices":[],"part":3,"_links":{"self":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/757","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/users\/5"}],"version-history":[{"count":30,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/757\/revisions"}],"predecessor-version":[{"id":1027,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/757\/revisions\/1027"}],"part":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/parts\/3"}],"metadata":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapters\/757\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/media?parent=757"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/pressbooks\/v2\/chapter-type?post=757"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/contributor?post=757"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/wp-json\/wp\/v2\/license?post=757"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}