Cancer Epigenetics: An Introduction

Kanwal, Rajnee; Gupta, Karishma; Gupta, Sanjay

doi:10.1007/978-1-4939-1804-1_1

Cited by 211 publications

(163 citation statements)

References 117 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…Therefore, it is necessary to thoroughly investigate the pathogenetic mechanism of HCC and develop new targeted treatments. The majority of recent investigations into cancer etiology have identified that epigenetics serves a critical role in cancer (27,28). Alterations in epigenetic modifications regulate all DNA-based processes, including transcription, DNA repair and replication, and are considered to be early events in tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Downregulated long non-coding RNA DREH promotes cell proliferation in hepatitis B virus-associated hepatocellular carcinoma

Wang

Zhang

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

The hepatitis B virus X (HBx) protein has been characterized as an oncogene involved in epigenetic modifications during hepatocarcinogenesis; however, the underlying mechanisms are not entirely clear. Long non-coding RNAs (lncRNAs), a type of epigenetic regulator molecules, have also been demonstrated to serve crucial roles in carcinogenesis, including hepatocellular carcinoma (HCC). In the present study, a human lncRNA DREH was identified, which inhibits cell proliferation in vitro and in vivo, and acts as a tumor suppressor in HBx-mediated hepatocarcinogenesis. The study revealed that the expression of DREH was frequently downregulated in hepatitis B virus (HBV)-associated HCC tissues in comparison with adjacent non-cancerous hepatic tissues, and was inversely correlated with HBx mRNA expression in HBV-associated HCC. In addition, the levels of DREH were inversely correlated with hepatitis B surface antigen and tumor size in HCC tissues. The forced expression of HBx in liver cell lines resulted in a significant decrease in the expression of DREH. Furthermore, suppression of DREH expression promotes the proliferation of HCC cells in vitro and in vivo. In conclusion, the present findings support the role of HBx-downregulated lncRNA DREH in tumor suppression in HBV-associated HCC patients. This contributes to a better understanding of epigenetic aberration of deregulated lncRNAs by HBx and the potential development of lncRNA-based targeted approaches for the treatment of HBV-associated HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulated long non-coding RNA DREH promotes cell proliferation in hepatitis B virus-associated hepatocellular carcinoma

Wang

Zhang

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…Notably, epigenetic modifications are known to precede genetic alterations in human neoplasms [57]. Therefore, we believe that the ENI plays a significant role in the initiating stages of NEPC trans-differentiation via epigenetic modification of downstream gene targets.…”

Section: The Epigenetic/non-coding Interactome and Its Implication Inmentioning

confidence: 94%

“…REST is part of the KDM1A-coREST-REST (Lysine-specific histone demethylase 1A-REST Corepressor 1-RE1-silencing transcription factor) histone modifying complex which is bound by HOTAIR, a long intergenic ncRNA that coordinates histone H3 lysine 27 methylation and lysine 4 demethylation [54]. Given that REST is commonly inactivated in NEPC and is responsible for repressing neuronal genes [55], aberrant silencing of this gene could trigger neuronal differentiation programs in trans-differentiating cells [56].Notably, epigenetic modifications are known to precede genetic alterations in human neoplasms [57]. Therefore, we believe that the ENI plays a significant role in the initiating stages of NEPC trans-differentiation via epigenetic modification of downstream gene targets.…”

mentioning

confidence: 99%

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

et al. 2016

View full text Add to dashboard Cite

Neuroendocrine prostate cancer (NEPC) is the most lethal prostatic neoplasm.NEPC is thought to originate from the trans-differentiation of AR-positive adenocarcinoma cells. We have previously shown that an epigenetic/non-coding interactome (ENI) orchestrates cancer cells' plasticity, thereby allowing the emergence of metastatic, drugresistant neoplasms. The primary objective of this manuscript is to discuss evidence indicating that some components of the ENI (Polycomb genes, microRNAs) play a key role in NEPC initiation and progression. Long non-coding RNAs (lncRNAs) represent vast and largely unexplored component of the ENI. Their role in NEPC has not been investigated. We show preliminary evidence indicating that a lncRNA (MIAT) is selectively up-regulated in NEPCs and might interact with Polycomb genes. Our results indicate that lncRNAs can be exploited as new biomarkers and therapeutic targets for NEPC.Keywords: Neuroendocrine prostate cancer; MIAT; Long non-coding RNAs; Polycomb; Epigenetic/non-coding interactome; Trans-differentiation. Neuroendocrine Prostate Cancer: Clinical and Molecular FeaturesIn adult males, the prostate is a small acorn-shaped tissue with ductal-acinar histology surrounding the urethra at the base of the bladder. Its main function is to contribute secretory proteins to the seminal fluid [1]. The adult prostate is a pseudo-stratified epithelium composed of three main cell lineages (Fig.1, left panel): 1) secretory luminal cells are the predominant cell type; these cells express keratins (K8, K18), the androgen receptor (AR) and secretory proteins such as prostate-specific antigen (PSA) and prostatic specific acid phosphatase (PSAP);2) basal cells expressing K5 and K14 keratins and p63 are the second major cell type;3) neuroendocrine cells (NEC) expressing chromogranin A (CHGA), synaptophysin (SYP), and neuropeptides are scattered throughout the basal layer and comprise less than 1% of normal prostatic glandular epithelium [1][2][3].Prostate cancer (PCa) represents the second most frequently diagnosed neoplasm and is the sixth leading cause of cancer-related deaths in males worldwide [4,5]. In keeping with the composition of prostate epithelium, more than 95% of PCas are classified as adenocarcinomas, which show luminal phenotype and AR expression [6] (Fig.1, middle panel).Endogenous androgens, mainly produced by the testis, bind to the AR and fuel prostate adenocarcinoma proliferation [7]. For this reason, androgen-deprivation therapy (a.k.a. castration) is an effective therapeutic strategy for this disease. However, patients invariably relapse despite castrate androgen levels (castration-resistant PCa, CRPC) mainly via genetic and epigenetic alterations that facilitate ligand-independent AR activation, amplify the ARdependent signaling, or trigger different proliferative pathways [7]. CRPCs are characterized by substantially worse prognoses, but chemotherapeutics and newly approved hormonal treatments (e.g., Enzalutamide [8] and Abiraterone [9]) are still effective in p...

show abstract

“…These evidence strongly supports the notion that epigenetic mechanisms may act as driving forces during carcinogenesis and support cancer cell survival and proliferation. Based on this notion, epigenetic regulatory enzymes are considered as important targets for cancer therapy 3 . Several drugs targeting DNA methylation and histone acetylation have been approved for cancer treatment in clinic 3 .…”

Section: Epigenetic Dysregulation In Cancermentioning

confidence: 99%

“…Based on this notion, epigenetic regulatory enzymes are considered as important targets for cancer therapy 3 . Several drugs targeting DNA methylation and histone acetylation have been approved for cancer treatment in clinic 3 . DNMT inhibitors, such as the cytidine analogues 5-azacytidine and 5-aza-2'deoxycytidine, can be incorporated into the daughter strands of DNA during DNA replication, which leads to DNA demethylation because This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction.…”

Section: Epigenetic Dysregulation In Cancermentioning

confidence: 99%

CRISPR/Cas9-Mediated Genome Editing of Epigenetic Factors for Cancer Therapy

Yao

Chen

2015

Human Gene Therapy

View full text Add to dashboard Cite

Advances in engineered recombinant nuclease have provided facile and reliable methods for genome editing. Especially with the development of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) system, the discovery of various versions of Cas9 proteins and delivery carriers, it is now practicable to introduce desired mutations into the genome, to correct disease-related mutations, and to activate or suppress genes of interest. Epigenetic regulators are often disturbed in cancer cells and are essential for the transformation of normal to cancerous cells. Tumor-related epigenetic alterations or epigenetic factor mutations play a major part during the various steps of carcinogenesis and affect a variety of cancer-related genes and a wide range of cancerous phenotypes. Therefore, epigenetic regulatory enzymes might be candidate targets for cancer therapy. In this review, we discuss prospects of CRISPR/Cas9-based genome editing in targeting epigenetics for cancer gene therapy.

show abstract

Cancer Epigenetics: An Introduction

Cited by 211 publications

References 117 publications

Downregulated long non-coding RNA DREH promotes cell proliferation in hepatitis B virus-associated hepatocellular carcinoma

Downregulated long non-coding RNA DREH promotes cell proliferation in hepatitis B virus-associated hepatocellular carcinoma

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

CRISPR/Cas9-Mediated Genome Editing of Epigenetic Factors for Cancer Therapy

Contact Info

Product

Resources

About