Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges

Abstract

Colorectal cancer, a leading cause of mortality worldwide, is a multistep disorder that results from the alteration of genetic and epigenetic mechanisms under contextual influence. Epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs, affect every aspect of tumor development from initiation to metastasis. Cancer stem cell promotion is also included in the wide spectrum of epigenetic dysregulations. Elucidation of this complex crosstalk network may offer new insights in the molecular interactions involved in the pathogenesis of colorectal carcinogenesis. In the era of translational medicine new horizons are opened for the pursuit of personalized therapeutic approaches and the development of novel and accurate diagnostic, prognostic and therapy-assessment markers. This review discusses the implications of epigenetic mechanisms in tumor biology and their applications "from bench to bedside".

Pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA or histone modification H3K9Me3

“…In particular, combinations of various blood-based biomarkers have shown promising results [10]. Alterations in the epigenetic control of DNA (DNA methylation, miRNA expression, and histone modifications) play a fundamental role in gene regulation and expression, and thereby in the carcinogenesis [11], and determinations of epigenetic alterations in the circulation have shown to be potential biomarkers in cancer [12]. A way to assess the epigenetic alterations associated with CRC is by determination of levels of circulating cell-free nucleosomes in plasma and serum.…”

MicroRNA‑539 inhibits colorectal cancer progression by directly targeting SOX4

“…Tumor progression in CRC is a multi-step process that involves alterations at the genetic and epigenetic level (31)(32)(33). Accumulated evidence has led to the view that miRNAs serve important functions in cancer formation and through the regulation of tumor cell proliferation, cycle, apoptosis, metastasis and angiogenesis (34-36).…”

Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

“…for example, global DNA hypomethylation mainly occurs in dinucleotide of cytosine guanine (CpG) within mobility and repetitive genome components, including satellite DNA sequence (pericentromeric regions), repetitive sequence of long interspersed nuclear element (LINE) and retrotransposon (39). Hypomethylation profile results in destruction of normal dinucleotide sequence and damage of chromosome stability through accumulating chromosome damage and inducing the reactivation of previously silenced genetic elements (retrotransposon), leading to the formation of various forms of cancer (40). A study has reported that miR-429 can target phosphatase and tensin homolog (PTEN) in endometrial cancer as a TSG and contribute to oncogenesis (41).…”