Histone Deacetylases and Their Regulatory MicroRNAs in Hepatocarcinogenesis

Kim, Hyung Seok; Shen, Qingyu; Nam, Suk Woo

doi:10.3346/jkms.2015.30.10.1375

Cited by 27 publications

(17 citation statements)

References 47 publications

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“… 108 The mechanisms underlying the dysregulation of HDAC expression in HCC are not fully understood, but a relevant role for specific miRNAs is clearly being elucidated. 105 , 109 A plethora of mechanistic studies have demonstrated the involvement of HDACs in the pathogenesis of HCC. When overexpressed, these epigenetic modifiers display multifaceted pro-oncogenic effects, including the inhibition of TSG expression, activation of cell cycle progression, apoptosis evasion, adaptation to hypoxia and metabolic reprogramming.…”

Section: Epigenetic Alterations In Hepatocarcinogenesismentioning

confidence: 99%

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

et al. 2020

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Summary Hepatocellular carcinoma (HCC) is a deadly tumour whose causative agents are generally well known, but whose pathogenesis remains poorly understood. Nevertheless, key genetic alterations are emerging from a heterogeneous molecular landscape, providing information on the tumorigenic process from initiation to progression. Among these molecular alterations, those that affect epigenetic processes are increasingly recognised as contributing to carcinogenesis from preneoplastic stages. The epigenetic machinery regulates gene expression through intertwined and partially characterised circuits involving chromatin remodelers, covalent DNA and histone modifications, and dedicated proteins reading these modifications. In this review, we summarise recent findings on HCC epigenetics, focusing mainly on changes in DNA and histone modifications and their carcinogenic implications. We also discuss the potential drugs that target epigenetic mechanisms for HCC treatment, either alone or in combination with current therapies, including immunotherapies.

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Section: Epigenetic Alterations In Hepatocarcinogenesismentioning

confidence: 99%

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

et al. 2020

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“…Since HDAC2 deregulation affects cell proliferation, apoptosis, and immune system in AML, focusing on specific miRNAs altered by this epigenetic regulator may identify potential markers for determining the best strategies in AML treatment. To date, many miRNAs were found directly targeted by HDAC2 in several cancers such as colorectal cancer , hepatocellular carcinoma , breast cancer , and AML . In AML, differentially expressed miRNAs have a prognostic and functional role associated with cytogenetics, molecular features, molecular markers, morphology, and clinical outcome .…”

Section: Discussionmentioning

confidence: 99%

HDAC2‐dependent miRNA signature in acute myeloid leukemia

et al. 2019

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Acute myeloid leukemia (AML) arises from a complex sequence of biological and finely orchestrated events that are still poorly understood. Increasingly, epigenetic studies are providing exciting findings that may be exploited in promising and personalized cutting‐edge therapies. A more appropriate and broader screening of possible players in cancer could identify a master molecular mechanism in AML. Here, we build on our previously published study by evaluating a histone deacetylase (HDAC)2‐mediated miRNA regulatory network in U937 leukemic cells. Following a comparative miRNA profiling analysis in genetically and enzymatically HDAC2‐downregulated AML cells, we identified miR‐96‐5p and miR‐92a‐3p as potential regulators in AML etiopathology by targeting defined genes. Our findings support the potentially beneficial role of alternative physiopathological interventions.

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“…Deregulation of miRNAs is known to facilitate cancer development by upregulating oncogenes or silencing tumor suppressor genes . MiRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri‐miRNAs) that can be either protein‐coding or non‐coding.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐495‐3p functions as a tumor suppressor by regulating multiple epigenetic modifiers in gastric carcinogenesis

Eun

Kim

Shen

et al. 2017

The Journal of Pathology

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MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Here, we demonstrate that microRNA-495-3p (miR-495-3p) functions as a potent tumor suppressor by governing ten oncogenic epigenetic modifiers (EMs) in gastric carcinogenesis. From the large cohort transcriptome datasets of gastric cancer (GC) patients available from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we were able to recapitulate 15 EMs as significantly overexpressed in GC among the 51 EMs that were previously reported to be involved in cancer progression. Computational target prediction yielded miR-495-3p, which targets as many as ten of the 15 candidate oncogenic EMs. Ectopic expression of miRNA mimics in GC cells caused miR-495-3p to suppress ten EMs, and inhibited tumor cell growth and proliferation via caspase-dependent and caspase-independent cell death processing. In addition, in vitro metastasis assays showed that miR-495-3p plays a role in the metastatic behavior of GC cells by regulating SLUG, vimentin, and N-cadherin. Furthermore, treatment of GC cells with 5-aza-2'-deoxcytidine restored miR-495-3p expression; sequence analysis revealed hypermethylation of the miR-495-3p promoter region in GC cells. A negative regulatory loop is proposed, whereby DNMT1, among ten oncogenic EMs, regulates miR-495-3p expression via hypermethylation of the miR-495-3p promoter. Our findings suggest that the functional loss or suppression of miR-495-3p triggers overexpression of multiple oncogenic EMs, and thereby contributes to malignant transformation and growth of gastric epithelial cells.

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Histone Deacetylases and Their Regulatory MicroRNAs in Hepatocarcinogenesis

Cited by 27 publications

References 47 publications

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

HDAC2‐dependent miRNA signature in acute myeloid leukemia

MicroRNA‐495‐3p functions as a tumor suppressor by regulating multiple epigenetic modifiers in gastric carcinogenesis

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