Epigenetic‐based therapy for colorectal cancer: Prospect and involved mechanisms

Abstract

Epigenetic modifications are heritable variations in gene expression not encoded by the DNA sequence. According to reports, a large number of studies have been performed to characterize epigenetic modification during normal development and also in cancer. Epigenetics can be regarded more widely to contain all of the changes in expression of genes that make by adjusted interactions between the regulatory portions of DNA or messenger RNAs that lead to indirect variation in the DNA sequence. In the last decade, epigenetic modification importance in colorectal cancer (CRC) pathogenesis was demonstrated powerfully. Although developments in CRC therapy have been made in the last years, much work is required as it remains the second leading cause of cancer death. Nowadays, epigenetic programs and genetic change have pivotal roles in the CRC incidence as well as progression. While our knowledge about epigenetic mechanism in CRC is not comprehensive, selective histone modifications and resultant chromatin conformation together with DNA methylation most likely regulate CRC pathogenesis that involved genes expression. Undoubtedly, the advanced understanding of epigenetic-based gene expression regulation in the CRC is essential to make epigenetic drugs for CRC therapy. The major aim of this review is to deliver a summary of valuable results that represent evidence of principle for epigeneticbased therapeutic approaches employment in CRC with a focus on the advantages of epigenetic-based therapy in the inhibition of the CRC metastasis and proliferation.

RETRACTED: The Role of Janus Kinase/STAT3 Pathway in Hematologic Malignancies With an Emphasis on Epigenetics

“…The discovery of the JAK/STAT pathway happened through a series of investigations looking into the relationship between interferon responses and signal transduction (Velazquez et al, 1992). The STAT family includes seven members: STAT1, STAT2, STAT3, STAT4, STAT5 (a/b), and STAT6 (Subramaniam et al, 2013;Rezapour et al, 2019). There is a standard structural pattern in all seven STAT proteins (Figure 1).…”

NK homeobox 2.2 functions as tumor suppressor in colorectal cancer due to DNA methylation

“…An inverse correlation was observed between the NKX2.2 methylation and its transcriptional levels. (2) No significant association was found between the NKX2.2 methylation and sex, age, tumor differentiation, TNM stage, CEA, CA199, and fecal occult blood.…”

“…DNA methylation was regarded to regulate the changes in expression of genes that make by adjusted interactions between DNA and messenger RNAs. In the past decades, methylation modification in CRC pathogenesis was demonstrated powerfully [2]. It was reported that NKX2.2 was dysregulated in a variety of cancers.…”

“…DNA methylation is a common epigenetic modification that has heritable variations in gene expression not encoded by the DNA sequence. A large number of studies have been reported to characterize methylation modification during the process of normal to CRC [2]. Nowadays, the methylation therapy is promising and deserved to explore furtherly in the CRC development as well as progression.…”

Regulation of signal transduction pathways in colorectal cancer: implications for therapeutic resistance

“…On top of non-coding RNAs-based regulation of therapeutic resistance in CRC, epigenetic changes that involve DNA methylation and histone modifications have also increasingly been reported ( Shen et al, 2018 ; Mahalakshmi, Husayn Ahmed & Mahadevan, 2018 ; Porcellini et al, 2018 ; Rezapour et al, 2019 ). For instances, hypermethylation of genes such as MEIS2 , SLFN11 and B4GALT1 are associated with cancer progression and resistance to chemotherapy (cisplatin or oxaliplatin-based therapy) and anti-EGFR therapy ( Baharudin et al, 2017 ; He et al, 2017 ; Picardo et al, 2019 ; Wang et al, 2019 ).…”