Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer
Identifieur interne : 000400 ( Pmc/Curation ); précédent : 000399; suivant : 000401Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer
Auteurs : Xin-Yue Gu [République populaire de Chine] ; Yang Jiang [République populaire de Chine] ; Ming-Qi Li [République populaire de Chine] ; Peng Han [République populaire de Chine] ; Yan-Long Liu [République populaire de Chine] ; Bin-Bin Cui [République populaire de Chine]Source :
- Aging (Albany NY) [ 1945-4589 ] ; 2020.
Abstract
A promising new strategy for cancer therapy is to target the autophagic pathway. However, comprehensive characterization of autophagy genes and their clinical relevance in cancer is still lacking. Here, we systematically characterized alterations of autophagy genes in multiple cancer lines by analyzing data from The Cancer Genome Atlas and CellMiner database. Interactions between autophagy genes and clinically actionable genes (CAGs) were identified by analyzing co-expression, protein-protein interactions (PPIs) and transcription factor (TF) data. A key subnetwork was identified that included 18 autophagy genes and 22 CAGs linked by 28 PPI pairs and 1 TF-target pair, which was EGFR targeted by RARA. Alterations in the expression of autophagy genes were associated with patient survival in multiple cancer types. RARA and EGFR were associated with worse survival in colorectal cancer patients. The regulatory role of EGFR in 5-FU resistance was validated in colon cancer cells in vivo and in vitro. EGFR contributed to 5-FU resistance in colon cancer cells through autophagy induction, and EGFR overexpression in 5-FU resistant colon cancer was regulated by RARA. The present study provides a comprehensive analysis of autophagy in different cancer cell lines and highlights the potential clinical utility of targeting autophagy genes.
Url:
DOI: 10.18632/aging.102607
PubMed: 31896739
PubMed Central: 6977699
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000400
Links to Exploration step
PMC:6977699Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer</title><author><name sortKey="Gu, Xin Yue" sort="Gu, Xin Yue" uniqKey="Gu X" first="Xin-Yue" last="Gu">Xin-Yue Gu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Yang" sort="Jiang, Yang" uniqKey="Jiang Y" first="Yang" last="Jiang">Yang Jiang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Pathology, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Li, Ming Qi" sort="Li, Ming Qi" uniqKey="Li M" first="Ming-Qi" last="Li">Ming-Qi Li</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Han, Peng" sort="Han, Peng" uniqKey="Han P" first="Peng" last="Han">Peng Han</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Yan Long" sort="Liu, Yan Long" uniqKey="Liu Y" first="Yan-Long" last="Liu">Yan-Long Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Cui, Bin Bin" sort="Cui, Bin Bin" uniqKey="Cui B" first="Bin-Bin" last="Cui">Bin-Bin Cui</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31896739</idno><idno type="pmc">6977699</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977699</idno><idno type="RBID">PMC:6977699</idno><idno type="doi">10.18632/aging.102607</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000400</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000400</idno><idno type="wicri:Area/Pmc/Curation">000400</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000400</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer</title><author><name sortKey="Gu, Xin Yue" sort="Gu, Xin Yue" uniqKey="Gu X" first="Xin-Yue" last="Gu">Xin-Yue Gu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Yang" sort="Jiang, Yang" uniqKey="Jiang Y" first="Yang" last="Jiang">Yang Jiang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Pathology, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Li, Ming Qi" sort="Li, Ming Qi" uniqKey="Li M" first="Ming-Qi" last="Li">Ming-Qi Li</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Han, Peng" sort="Han, Peng" uniqKey="Han P" first="Peng" last="Han">Peng Han</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Yan Long" sort="Liu, Yan Long" uniqKey="Liu Y" first="Yan-Long" last="Liu">Yan-Long Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author><author><name sortKey="Cui, Bin Bin" sort="Cui, Bin Bin" uniqKey="Cui B" first="Bin-Bin" last="Cui">Bin-Bin Cui</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040</wicri:regionArea></affiliation></author></analytic><series><title level="j">Aging (Albany NY)</title><idno type="eISSN">1945-4589</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A promising new strategy for cancer therapy is to target the autophagic pathway. However, comprehensive characterization of autophagy genes and their clinical relevance in cancer is still lacking. Here, we systematically characterized alterations of autophagy genes in multiple cancer lines by analyzing data from The Cancer Genome Atlas and CellMiner database. Interactions between autophagy genes and clinically actionable genes (CAGs) were identified by analyzing co-expression, protein-protein interactions (PPIs) and transcription factor (TF) data. A key subnetwork was identified that included 18 autophagy genes and 22 CAGs linked by 28 PPI pairs and 1 TF-target pair, which was EGFR targeted by RARA. Alterations in the expression of autophagy genes were associated with patient survival in multiple cancer types. RARA and EGFR were associated with worse survival in colorectal cancer patients. The regulatory role of EGFR in 5-FU resistance was validated in colon cancer cells in vivo and in vitro. EGFR contributed to 5-FU resistance in colon cancer cells through autophagy induction, and EGFR overexpression in 5-FU resistant colon cancer was regulated by RARA. The present study provides a comprehensive analysis of autophagy in different cancer cell lines and highlights the potential clinical utility of targeting autophagy genes.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Aging (Albany NY)</journal-id><journal-id journal-id-type="iso-abbrev">Aging (Albany NY)</journal-id><journal-id journal-id-type="publisher-id">Aging</journal-id><journal-title-group><journal-title>Aging (Albany NY)</journal-title></journal-title-group><issn pub-type="epub">1945-4589</issn><publisher><publisher-name>Impact Journals</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31896739</article-id><article-id pub-id-type="pmc">6977699</article-id><article-id pub-id-type="doi">10.18632/aging.102607</article-id><article-id pub-id-type="publisher-id">102607</article-id><article-id pub-id-type="publisher-id">102607</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gu</surname><given-names>Xin-Yue</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="F1">*</xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Yang</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="F1">*</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Ming-Qi</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="F1">*</xref></contrib><contrib contrib-type="author"><name><surname>Han</surname><given-names>Peng</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Yan-Long</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Cui</surname><given-names>Bin-Bin</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><aff id="aff1"><label>1</label>Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</aff><aff id="aff2"><label>2</label>Department of Pathology, Harbin Medical University Cancer Hospital, Harbin 150040, People’s Republic of China</aff></contrib-group><author-notes><fn fn-type="equal" id="F1"><label>*</label><p id="P1">Equal contribution</p></fn><corresp id="cor1"><bold>Correspondence to:</bold> Bin-Bin Cui; <bold>email:</bold> cbb2888@163.com</corresp></author-notes><pub-date pub-type="collection"><day>15</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="epub"><day>02</day><month>1</month><year>2020</year></pub-date><volume>12</volume><issue>1</issue><fpage>156</fpage><lpage>177</lpage><history><date date-type="received"><day>18</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>05</day><month>12</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2020 Gu et al.</copyright-statement><license specific-use="CC BY 3.0" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>A promising new strategy for cancer therapy is to target the autophagic pathway. However, comprehensive characterization of autophagy genes and their clinical relevance in cancer is still lacking. Here, we systematically characterized alterations of autophagy genes in multiple cancer lines by analyzing data from The Cancer Genome Atlas and CellMiner database. Interactions between autophagy genes and clinically actionable genes (CAGs) were identified by analyzing co-expression, protein-protein interactions (PPIs) and transcription factor (TF) data. A key subnetwork was identified that included 18 autophagy genes and 22 CAGs linked by 28 PPI pairs and 1 TF-target pair, which was EGFR targeted by RARA. Alterations in the expression of autophagy genes were associated with patient survival in multiple cancer types. RARA and EGFR were associated with worse survival in colorectal cancer patients. The regulatory role of EGFR in 5-FU resistance was validated in colon cancer cells in vivo and in vitro. EGFR contributed to 5-FU resistance in colon cancer cells through autophagy induction, and EGFR overexpression in 5-FU resistant colon cancer was regulated by RARA. The present study provides a comprehensive analysis of autophagy in different cancer cell lines and highlights the potential clinical utility of targeting autophagy genes.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords:</title><kwd>autophagy</kwd><kwd>drug sensitivity</kwd><kwd>EGFR</kwd><kwd>5-fluorouracil</kwd></kwd-group></article-meta><notes><def-list list-type="simple" list-content="abbreviations"><title>Abbreviations</title><def-item><term>ATG</term><def><p>Autophagy-related genes</p></def></def-item><def-item><term>ChIP</term><def><p>Chromatin immunoprecipitation</p></def></def-item><def-item><term>AO/EB staining</term><def><p>Acridine Orange/Ethidium Bromide staining</p></def></def-item><def-item><term>EGFR</term><def><p>Epidermal growth factor receptor</p></def></def-item><def-item><term>RARA</term><def><p>Retinoic acid receptor-α</p></def></def-item><def-item><term>CAGs</term><def><p>Clinically actionable genes</p></def></def-item><def-item><term>PPIs</term><def><p>Protein-protein interactions</p></def></def-item><def-item><term>TF</term><def><p>Transcription factor</p></def></def-item><def-item><term>PCC</term><def><p>Pearson correlation coefficient</p></def></def-item><def-item><term>STAD</term><def><p>Stomach adenocarcinoma</p></def></def-item><def-item><term>LGG</term><def><p>Lower grade glioma</p></def></def-item><def-item><term>BLCA</term><def><p>Bladder urothelial carcinoma</p></def></def-item><def-item><term>KIRP</term><def><p>Kidney renal papillary cell carcinoma</p></def></def-item><def-item><term>PI3K</term><def><p>Phosphatidylinositide 3 kinase</p></def></def-item></def-list></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000400 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000400 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:6977699
|texte= Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:31896739" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |