Cancer induction and suppression with transcriptional control and epigenome editing technologies

Abstract

Cancer epigenetics is one of the most important research subjects in dissecting cancer mechanisms and therapeutic targets because the emergence and malignant transformation of various cancers are caused by unnatural expression of cancer-related genes attributed to their epigenetic errors. The original concept of cancer epigenetics basically stands on the analysis of the epigenetic status in naturally occurring cancer cells; however, the rapidly emerging technology called epigenome editing would change this situation drastically. Epigenome editing, the most promising derivative technology of genome editing, can modify the epigenetic states at the pre-defined genomic locus using the programmable effectors, consisting of various epigenetic factors combined with site-specific DNA-binding domains. This technology can be utilized in a reversible manner; i.e., cancer modeling can be achieved by introducing aberrant epigenetic marks in normal cells, and cancer suppression can be achieved by correcting the epigenetic errors in cancer cells. In this review, we summarize the basics of epigenome editing and cancer epigenetics, followed by the current examples of cancer induction and suppression with the transcriptional control and epigenome editing technologies.

MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer

“…The basic structure of editing tools includes a programmable DNA-binding domain and an epigenetic effector domain of interest. Three different programmable DNA-recognition domains have been reported widely in epigenome editing, including the zinc finger (ZF), transcription activator-like effector (TALE), and nuclease-deficient Cas9 (dCas9) [249]. The epigenetic effectors are rather diverse ranging from the reader and erasure of DNA and histone modification marks as well as artificial transcription factors [250].…”

Targeting Epigenetic Modifications in Uveal Melanoma

“…The fundamental structure of editing tools includes a programmable DNA-binding domain and an epigenetic effector domain of interest. The zinc finger nucleases (ZFN), transcription activator-like effector (TALE), and nuclease-deficient Cas9 (dCas9) are three different programmable DNA-recognition domains which have been broadly used in epigenome editing, the most promising derivative technology of genome editing [ 120 ]. The epigenetic effectors are diverse, ranging from the writers, erasers, and readers, depositing, removing, or detecting DNA and histone modification marks as well as artificial transcription factors [ 121 ].…”

Acceleration of cancer science with genome editing and related technologies

“…In addition, direct conversion of epigenetic status has been achieved by epigenetic modification enzymes fused with dCas9 or other related systems. We recently summarized the technical background of such transcriptional control and epigenome editing technologies and their application in cancer science; therefore, the several newest investigations in this context that were not published at the time of publication of the previous review are only introduced in the present article.…”