Modulating epigenetic modifications for cancer therapy (Review)

Abstract

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non-coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resistance in cancer. The present review describes central epigenetic aberrations during malignant transformation and explains how epidrugs target DNA methylation, histone modifications and ncRNAs. Furthermore, clinical trials focused on evaluating the effect of these epidrugs alone or in combination with other anticancer therapies and other ncRNA-based therapies are discussed. The use of epidrugs promises to be an effective tool for reversing drug resistance in some patients with cancer. Contents1. Introduction 2. Epigenetic mechanisms in cancer, roles in carcinogenesis and therapeutic approaches 3. ncRNAs in epigenetic control 4. Conclusions

The Transcription Factor NRF2 Has Epigenetic Regulatory Functions Modulating HDACs, DNMTs, and miRNA Biogenesis

“…The results presented in this study can be potentially relevant to a wide range of pathologies where epigenetic mechanisms are of particular importance, such as cancer [ 52 , 53 ], allergies [ 54 ] , and neurodegenerative diseases [ 55 , 56 ]. In cancer, specific methylation and other alterations of the NFE2L2 promoter have been documented [ 12 , 57 , 58 ], which can alter the expression levels of NRF2, linked to carcinogenesis through metabolic reprogramming, tumor promotion, inflammation, and resistance to therapy.…”

Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance

“…In general, the epigenetic regulatory mechanisms of BMSCs are not well understood, and research on epigenetic drugs is mainly focused on cancer treatments; for example, by reprogramming the cancer epigenome in an attempt to reverse drug resistance. 124 DNMT inhibitors are currently used as epigenetic drugs; they can also regulate the process of osteogenesis. Chen et al 125 reported that 5-aza-2′-deoxycytidine promotes bone production by upregulating the demethylation of WNT10A and osteogenic markers; it is also associated with dosedependent levels of DLX5 and OSX promoter demethylation.…”

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

“…Finally, miR-122 is also considered a tumor suppressor for HCC, while it is quite plentiful liver-specific miRNA that has a pivotal role in lipid metabolism [ 61 ]. This miRNA is commonly downregulated in HCC tissues, whereas it has been reported that the knockdown of miR-122 leads to steatohepatitis and hepatocarcinogenesis [ 62 ]. The aforementioned phenomenon is mainly attributed to the indirect activation of p53 via targeting its regulator, the so-called mouse double minute 2 homolog (mdm2) [ 63 ].…”

“…An example of utilizing miRNA targets is the attempt of enhancing the tumor-suppressing effect of miR-122, which targets ADAM10, IGF1R, as well as cyclin G1 and ADAM17. Meanwhile, the suppression of the aforementioned targets could also enhance the expression levels of miR-122 [ 62 ].…”