Abstract
Cancer can be identified as a chaotic cell state, which breaks the rules that govern growth and reproduction, with main characteristics such as uncontrolled division, invading other tissues, usurping resources, and eventually killing its host. It was once believed that cancer is caused by a progressive series of genetic aberrations, and certain mutations of genes, including oncogenes and tumor suppressor genes, have been identified as the cause of cancer. However, piling evidence suggests that epigenetic modifications working in concert with genetic mechanisms to regulate transcriptional activity are dysregulated in many diseases, including cancer. Cancer epigenetics explain a wide range of heritable changes in gene expression, which do not come from any alteration in DNA sequences. Aberrant DNA methylation, histone modifications, and expression of long non-coding RNAs (lncRNAs) are key epigenetic mechanisms associated with tumor initiation, cancer progression, and metastasis. Within the past decade, cancer epigenetics have enabled us to develop novel biomarkers and therapeutic target for many types of cancers. In this review, we will summarize the major epigenetic changes involved in cancer biology along with clinical and preclinical results developed as novel cancer therapeutics.
Highlights
According to the Centers for Disease Control and Prevention (CDC), cancer is the second leading cause of death in the top ten diseases, next to heart disease (Heron et al 2012)
Piling evidence suggests that epigenetic modifications working in concert with genetic mechanisms to regulate transcriptional activity are dysregulated in many diseases, including cancer
Aberrant DNA methylation, histone modifications, and expression of long non-coding RNAs are key epigenetic mechanisms associated with tumor initiation, cancer progression, and metastasis
Summary
According to the Centers for Disease Control and Prevention (CDC), cancer is the second leading cause of death in the top ten diseases, next to heart disease (Heron et al 2012). BCR-ABL1 fusion oncoprotein is a constitutively active tyrosine kinase signaling protein, causing the cell to divide uncontrollably and develop CML Ras mutation is another most well-known gain-offunction mutation identified in human cancer (Bos 1989; Fernandez-Medarde and Santos 2011; Prior et al 2012). Altered gene expression in cancer through epigenetic pathways is very complex and is determined by chromatin structure changes, including DNA methylation, histone variants and various modifications, nucleosome remodeling, and small non-coding RNAs (Dawson and Kouzarides 2012). Similar to other epigenetic modifications, histone methylation is regulated by writer (lysine methyltransferases: KMTs), reader, and eraser (lysine demethylases: KDMs) proteins. As epigenetic readers of arginine methylation, Tudor domain-containing proteins, such as SMN (Survival of motor neuron), SPF30 (Splicing factor 30), and TDRD1/2/ 3/6/9/11, have been identified to interact with methylarginine residues (Gayatri and Bedford 2014).
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