Loading…
New insights on the role of epigenetic alterations in hepatocellular carcinoma
Emerging evidence assigns to epigenetic mechanisms heritable differences in gene function that come into being during cell development or via the effect of environmental factors. Epigenetic deregulation is strongly involved in the development of hepatocellular carcinoma (HCC). It includes changes in...
Saved in:
Published in: | Journal of hepatocellular carcinoma 2014-01, Vol.1 (Issue 1), p.65-83 |
---|---|
Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | |
---|---|
cites | |
container_end_page | 83 |
container_issue | Issue 1 |
container_start_page | 65 |
container_title | Journal of hepatocellular carcinoma |
container_volume | 1 |
creator | Frau, Maddalena Feo, Claudio F Feo, Francesco Pascale, Rosa M |
description | Emerging evidence assigns to epigenetic mechanisms heritable differences in gene function that come into being during cell development or via the effect of environmental factors. Epigenetic deregulation is strongly involved in the development of hepatocellular carcinoma (HCC). It includes changes in methionine metabolism, promoter hypermethylation, or increased proteasomal degradation of oncosuppressors, as well as posttranscriptional deregulation by microRNA or messenger RNA (mRNA) binding proteins. Alterations in the methylation of the promoter of methyl adenosyltransferase MAT1A and MAT2A genes in HCC result in decreased S-adenosylmethionine levels, global DNA hypomethylation, and deregulation of signal transduction pathways linked to methionine metabolism and methyl adenosyltransferases activity. Changes in S-adenosylmethionine levels may also depend on MAT1A mRNA destabilization associated with MAT2A mRNA stabilization by specific proteins. Decrease in MAT1A expression has also been attributed to miRNA upregulation in HCC. A complex deregulation of miRNAs is also strongly involved in hepatocarcinogenesis, with up-regulation of different miRNAs targeting oncosuppressor genes and down-regulation of miRNAs targeting genes involved in cell-cycle and signal transduction control. Oncosuppressor gene down-regulation in HCC is also induced by promoter hypermethylation or posttranslational deregulation, leading to proteasomal degradation. The role of epigenetic changes in hepatocarcinogenesis has recently suggested new promising therapeutic approaches for HCC on the basis of the administration of methylating agents, inhibition of methyl adenosyltransferases, and restoration of the expression of tumor-suppressor miRNAs. |
doi_str_mv | 10.2147/JHC.S44506 |
format | article |
fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_bd1ecd1c8a874494958467a7e119547f</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_bd1ecd1c8a874494958467a7e119547f</doaj_id><sourcerecordid>1810865979</sourcerecordid><originalsourceid>FETCH-LOGICAL-c361t-54d3ebb73b42f15b48c855cfa8b4b3bf504153ad38449d2f96697fbcd8855e43</originalsourceid><addsrcrecordid>eNpdkU1LXDEUhkOpVFE3_QHlQjelMDafN8mmUIZaLaIL3Yck99yZDHeSaZJr6b83dqxos8nXw8PLeRF6T_AZJVx--XmxPLvlXOD-DTqiVLCF0L1---J8iE5L2WCMSbthqd6hQyoFVkTKI3R9Db-7EEtYrWvpUuzqGrqcJujS2MEurCBCDb6zU4Vsa0ixNLxbw87W5GGa5snmztvsQ0xbe4IORjsVOH3aj9Hd-fe75cXi6ubH5fLb1cKzntSF4AMD5yRznI5EOK68EsKPVjnumBsF5kQwOzDFuR7oqPtey9H5QTUMODtGl3vtkOzG7HLY2vzHJBvM34eUV8bmFnsC4wYCfiBeWSWbjGuheC-tBEK04HJsrq971252Wxg8xJrt9Er6-ieGtVmle8M1UVTSJvj0JMjp1wylmm0oj6OxEdJcDFEEq15oqRv68T90k-Yc26QMbQtz0Xpp1Oc95XMqJcP4HIZg81i6aaWbfekN_vAy_jP6r2L2AOKwpvw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2222045508</pqid></control><display><type>article</type><title>New insights on the role of epigenetic alterations in hepatocellular carcinoma</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Frau, Maddalena ; Feo, Claudio F ; Feo, Francesco ; Pascale, Rosa M</creator><creatorcontrib>Frau, Maddalena ; Feo, Claudio F ; Feo, Francesco ; Pascale, Rosa M</creatorcontrib><description>Emerging evidence assigns to epigenetic mechanisms heritable differences in gene function that come into being during cell development or via the effect of environmental factors. Epigenetic deregulation is strongly involved in the development of hepatocellular carcinoma (HCC). It includes changes in methionine metabolism, promoter hypermethylation, or increased proteasomal degradation of oncosuppressors, as well as posttranscriptional deregulation by microRNA or messenger RNA (mRNA) binding proteins. Alterations in the methylation of the promoter of methyl adenosyltransferase MAT1A and MAT2A genes in HCC result in decreased S-adenosylmethionine levels, global DNA hypomethylation, and deregulation of signal transduction pathways linked to methionine metabolism and methyl adenosyltransferases activity. Changes in S-adenosylmethionine levels may also depend on MAT1A mRNA destabilization associated with MAT2A mRNA stabilization by specific proteins. Decrease in MAT1A expression has also been attributed to miRNA upregulation in HCC. A complex deregulation of miRNAs is also strongly involved in hepatocarcinogenesis, with up-regulation of different miRNAs targeting oncosuppressor genes and down-regulation of miRNAs targeting genes involved in cell-cycle and signal transduction control. Oncosuppressor gene down-regulation in HCC is also induced by promoter hypermethylation or posttranslational deregulation, leading to proteasomal degradation. The role of epigenetic changes in hepatocarcinogenesis has recently suggested new promising therapeutic approaches for HCC on the basis of the administration of methylating agents, inhibition of methyl adenosyltransferases, and restoration of the expression of tumor-suppressor miRNAs.</description><identifier>ISSN: 2253-5969</identifier><identifier>EISSN: 2253-5969</identifier><identifier>DOI: 10.2147/JHC.S44506</identifier><identifier>PMID: 27508177</identifier><language>eng</language><publisher>New Zealand: Taylor & Francis Ltd</publisher><subject>DNA methylation ; Epigenetics ; hepatocarcinogenesis ; Kinases ; Liver cancer ; microRNA ; prognosis ; progression ; Review ; signal transduction ; therapeutic targets</subject><ispartof>Journal of hepatocellular carcinoma, 2014-01, Vol.1 (Issue 1), p.65-83</ispartof><rights>2014. This work is licensed under https://creativecommons.org/licenses/by-nc/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Frau et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2222045508/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2222045508?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27508177$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Frau, Maddalena</creatorcontrib><creatorcontrib>Feo, Claudio F</creatorcontrib><creatorcontrib>Feo, Francesco</creatorcontrib><creatorcontrib>Pascale, Rosa M</creatorcontrib><title>New insights on the role of epigenetic alterations in hepatocellular carcinoma</title><title>Journal of hepatocellular carcinoma</title><addtitle>J Hepatocell Carcinoma</addtitle><description>Emerging evidence assigns to epigenetic mechanisms heritable differences in gene function that come into being during cell development or via the effect of environmental factors. Epigenetic deregulation is strongly involved in the development of hepatocellular carcinoma (HCC). It includes changes in methionine metabolism, promoter hypermethylation, or increased proteasomal degradation of oncosuppressors, as well as posttranscriptional deregulation by microRNA or messenger RNA (mRNA) binding proteins. Alterations in the methylation of the promoter of methyl adenosyltransferase MAT1A and MAT2A genes in HCC result in decreased S-adenosylmethionine levels, global DNA hypomethylation, and deregulation of signal transduction pathways linked to methionine metabolism and methyl adenosyltransferases activity. Changes in S-adenosylmethionine levels may also depend on MAT1A mRNA destabilization associated with MAT2A mRNA stabilization by specific proteins. Decrease in MAT1A expression has also been attributed to miRNA upregulation in HCC. A complex deregulation of miRNAs is also strongly involved in hepatocarcinogenesis, with up-regulation of different miRNAs targeting oncosuppressor genes and down-regulation of miRNAs targeting genes involved in cell-cycle and signal transduction control. Oncosuppressor gene down-regulation in HCC is also induced by promoter hypermethylation or posttranslational deregulation, leading to proteasomal degradation. The role of epigenetic changes in hepatocarcinogenesis has recently suggested new promising therapeutic approaches for HCC on the basis of the administration of methylating agents, inhibition of methyl adenosyltransferases, and restoration of the expression of tumor-suppressor miRNAs.</description><subject>DNA methylation</subject><subject>Epigenetics</subject><subject>hepatocarcinogenesis</subject><subject>Kinases</subject><subject>Liver cancer</subject><subject>microRNA</subject><subject>prognosis</subject><subject>progression</subject><subject>Review</subject><subject>signal transduction</subject><subject>therapeutic targets</subject><issn>2253-5969</issn><issn>2253-5969</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkU1LXDEUhkOpVFE3_QHlQjelMDafN8mmUIZaLaIL3Yck99yZDHeSaZJr6b83dqxos8nXw8PLeRF6T_AZJVx--XmxPLvlXOD-DTqiVLCF0L1---J8iE5L2WCMSbthqd6hQyoFVkTKI3R9Db-7EEtYrWvpUuzqGrqcJujS2MEurCBCDb6zU4Vsa0ixNLxbw87W5GGa5snmztvsQ0xbe4IORjsVOH3aj9Hd-fe75cXi6ubH5fLb1cKzntSF4AMD5yRznI5EOK68EsKPVjnumBsF5kQwOzDFuR7oqPtey9H5QTUMODtGl3vtkOzG7HLY2vzHJBvM34eUV8bmFnsC4wYCfiBeWSWbjGuheC-tBEK04HJsrq971252Wxg8xJrt9Er6-ieGtVmle8M1UVTSJvj0JMjp1wylmm0oj6OxEdJcDFEEq15oqRv68T90k-Yc26QMbQtz0Xpp1Oc95XMqJcP4HIZg81i6aaWbfekN_vAy_jP6r2L2AOKwpvw</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Frau, Maddalena</creator><creator>Feo, Claudio F</creator><creator>Feo, Francesco</creator><creator>Pascale, Rosa M</creator><general>Taylor & Francis Ltd</general><general>Dove Medical Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140101</creationdate><title>New insights on the role of epigenetic alterations in hepatocellular carcinoma</title><author>Frau, Maddalena ; Feo, Claudio F ; Feo, Francesco ; Pascale, Rosa M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-54d3ebb73b42f15b48c855cfa8b4b3bf504153ad38449d2f96697fbcd8855e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>DNA methylation</topic><topic>Epigenetics</topic><topic>hepatocarcinogenesis</topic><topic>Kinases</topic><topic>Liver cancer</topic><topic>microRNA</topic><topic>prognosis</topic><topic>progression</topic><topic>Review</topic><topic>signal transduction</topic><topic>therapeutic targets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frau, Maddalena</creatorcontrib><creatorcontrib>Feo, Claudio F</creatorcontrib><creatorcontrib>Feo, Francesco</creatorcontrib><creatorcontrib>Pascale, Rosa M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest_Research Library</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of hepatocellular carcinoma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frau, Maddalena</au><au>Feo, Claudio F</au><au>Feo, Francesco</au><au>Pascale, Rosa M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New insights on the role of epigenetic alterations in hepatocellular carcinoma</atitle><jtitle>Journal of hepatocellular carcinoma</jtitle><addtitle>J Hepatocell Carcinoma</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>1</volume><issue>Issue 1</issue><spage>65</spage><epage>83</epage><pages>65-83</pages><issn>2253-5969</issn><eissn>2253-5969</eissn><abstract>Emerging evidence assigns to epigenetic mechanisms heritable differences in gene function that come into being during cell development or via the effect of environmental factors. Epigenetic deregulation is strongly involved in the development of hepatocellular carcinoma (HCC). It includes changes in methionine metabolism, promoter hypermethylation, or increased proteasomal degradation of oncosuppressors, as well as posttranscriptional deregulation by microRNA or messenger RNA (mRNA) binding proteins. Alterations in the methylation of the promoter of methyl adenosyltransferase MAT1A and MAT2A genes in HCC result in decreased S-adenosylmethionine levels, global DNA hypomethylation, and deregulation of signal transduction pathways linked to methionine metabolism and methyl adenosyltransferases activity. Changes in S-adenosylmethionine levels may also depend on MAT1A mRNA destabilization associated with MAT2A mRNA stabilization by specific proteins. Decrease in MAT1A expression has also been attributed to miRNA upregulation in HCC. A complex deregulation of miRNAs is also strongly involved in hepatocarcinogenesis, with up-regulation of different miRNAs targeting oncosuppressor genes and down-regulation of miRNAs targeting genes involved in cell-cycle and signal transduction control. Oncosuppressor gene down-regulation in HCC is also induced by promoter hypermethylation or posttranslational deregulation, leading to proteasomal degradation. The role of epigenetic changes in hepatocarcinogenesis has recently suggested new promising therapeutic approaches for HCC on the basis of the administration of methylating agents, inhibition of methyl adenosyltransferases, and restoration of the expression of tumor-suppressor miRNAs.</abstract><cop>New Zealand</cop><pub>Taylor & Francis Ltd</pub><pmid>27508177</pmid><doi>10.2147/JHC.S44506</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2253-5969 |
ispartof | Journal of hepatocellular carcinoma, 2014-01, Vol.1 (Issue 1), p.65-83 |
issn | 2253-5969 2253-5969 |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_bd1ecd1c8a874494958467a7e119547f |
source | Publicly Available Content Database; PubMed Central |
subjects | DNA methylation Epigenetics hepatocarcinogenesis Kinases Liver cancer microRNA prognosis progression Review signal transduction therapeutic targets |
title | New insights on the role of epigenetic alterations in hepatocellular carcinoma |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T13%3A34%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20insights%20on%20the%20role%20of%20epigenetic%20alterations%20in%20hepatocellular%20carcinoma&rft.jtitle=Journal%20of%20hepatocellular%20carcinoma&rft.au=Frau,%20Maddalena&rft.date=2014-01-01&rft.volume=1&rft.issue=Issue%201&rft.spage=65&rft.epage=83&rft.pages=65-83&rft.issn=2253-5969&rft.eissn=2253-5969&rft_id=info:doi/10.2147/JHC.S44506&rft_dat=%3Cproquest_doaj_%3E1810865979%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c361t-54d3ebb73b42f15b48c855cfa8b4b3bf504153ad38449d2f96697fbcd8855e43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2222045508&rft_id=info:pmid/27508177&rfr_iscdi=true |