Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis.
Identifieur interne : 000376 ( Main/Corpus ); précédent : 000375; suivant : 000377Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis.
Auteurs : Shan-Ying Wu ; Sheng-Hui Lan ; Hsiao-Sheng LiuSource :
- Autophagy [ 1554-8635 ] ; 2019.
English descriptors
- KwdEn :
- MESH :
- chemical : Cyclin D1, MicroRNAs.
- Animals, Autophagy, Carcinogenesis, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Mice.
Abstract
Overexpressed CCND1 (cyclin D1) is associated with hepatocellular carcinoma (HCC) and we used 147 tumor tissue samples from HCC patients and 3 murine models to reveal an inverse correlation between low autophagic activity and high CCND1 expression. These 2 phenomena in combination correlated with poor overall survival in HCC patients. Mechanistic analysis showed that activated autophagy triggered CCND1 ubiquitination followed by SQSTM1 (sequestosome 1)-mediated selective phagophore recruitment, autophagosome formation, fusion with a lysosome, and degradation. Functional studies revealed that autophagy-selective degradation of CCND1 suppresses DNA synthesis, cell proliferation, and colony, and liver tumor formation by arresting the cell cycle at the G1 phase. Most importantly, diverse pharmacological inducers (rapamycin and amiodarone) effectively suppress tumor growth in orthotopic liver tumor and subcutaneous tumor xenograft models. In conclusion, we have demonstrated a link between degradative autophagy and the cell cycle regulator CCND1, and have discovered the underlying mechanism by which the autophagic degradation machinery regulates the turnover of the cell-cycle regulator CCND1, which in turn affects HCC tumorigenesis. Abbreviations: CCDN1: cyclin D1; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; SQSTM1: sequestosome 1.
DOI: 10.1080/15548627.2019.1569918
PubMed: 30646811
PubMed Central: PMC6526824
Links to Exploration step
pubmed:30646811Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis.</title><author><name sortKey="Wu, Shan Ying" sort="Wu, Shan Ying" uniqKey="Wu S" first="Shan-Ying" last="Wu">Shan-Ying Wu</name><affiliation><nlm:affiliation>a Department of Human Development and Family Studies , National Taiwan Normal University , Taipei , Taiwan.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>b Department of Microbiology and Immunology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.</nlm:affiliation></affiliation></author><author><name sortKey="Lan, Sheng Hui" sort="Lan, Sheng Hui" uniqKey="Lan S" first="Sheng-Hui" last="Lan">Sheng-Hui Lan</name><affiliation><nlm:affiliation>c Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences , China Medical University , Taichung , Taiwan.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Hsiao Sheng" sort="Liu, Hsiao Sheng" uniqKey="Liu H" first="Hsiao-Sheng" last="Liu">Hsiao-Sheng Liu</name><affiliation><nlm:affiliation>b Department of Microbiology and Immunology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>d Institute of Basic Medical Sciences, College of Medicine , National Cheng Kung University , Tainan , Taiwan.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30646811</idno><idno type="pmid">30646811</idno><idno type="doi">10.1080/15548627.2019.1569918</idno><idno type="pmc">PMC6526824</idno><idno type="wicri:Area/Main/Corpus">000376</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000376</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis.</title><author><name sortKey="Wu, Shan Ying" sort="Wu, Shan Ying" uniqKey="Wu S" first="Shan-Ying" last="Wu">Shan-Ying Wu</name><affiliation><nlm:affiliation>a Department of Human Development and Family Studies , National Taiwan Normal University , Taipei , Taiwan.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>b Department of Microbiology and Immunology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.</nlm:affiliation></affiliation></author><author><name sortKey="Lan, Sheng Hui" sort="Lan, Sheng Hui" uniqKey="Lan S" first="Sheng-Hui" last="Lan">Sheng-Hui Lan</name><affiliation><nlm:affiliation>c Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences , China Medical University , Taichung , Taiwan.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Hsiao Sheng" sort="Liu, Hsiao Sheng" uniqKey="Liu H" first="Hsiao-Sheng" last="Liu">Hsiao-Sheng Liu</name><affiliation><nlm:affiliation>b Department of Microbiology and Immunology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>d Institute of Basic Medical Sciences, College of Medicine , National Cheng Kung University , Tainan , Taiwan.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Autophagy</title><idno type="eISSN">1554-8635</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Autophagy (MeSH)</term><term>Carcinogenesis (MeSH)</term><term>Carcinoma, Hepatocellular (MeSH)</term><term>Cyclin D1 (MeSH)</term><term>Humans (MeSH)</term><term>Liver Neoplasms (MeSH)</term><term>Mice (MeSH)</term><term>MicroRNAs (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Cyclin D1</term><term>MicroRNAs</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Autophagy</term><term>Carcinogenesis</term><term>Carcinoma, Hepatocellular</term><term>Humans</term><term>Liver Neoplasms</term><term>Mice</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Overexpressed CCND1 (cyclin D1) is associated with hepatocellular carcinoma (HCC) and we used 147 tumor tissue samples from HCC patients and 3 murine models to reveal an inverse correlation between low autophagic activity and high CCND1 expression. These 2 phenomena in combination correlated with poor overall survival in HCC patients. Mechanistic analysis showed that activated autophagy triggered CCND1 ubiquitination followed by SQSTM1 (sequestosome 1)-mediated selective phagophore recruitment, autophagosome formation, fusion with a lysosome, and degradation. Functional studies revealed that autophagy-selective degradation of CCND1 suppresses DNA synthesis, cell proliferation, and colony, and liver tumor formation by arresting the cell cycle at the G<sub>1</sub> phase. Most importantly, diverse pharmacological inducers (rapamycin and amiodarone) effectively suppress tumor growth in orthotopic liver tumor and subcutaneous tumor xenograft models. In conclusion, we have demonstrated a link between degradative autophagy and the cell cycle regulator CCND1, and have discovered the underlying mechanism by which the autophagic degradation machinery regulates the turnover of the cell-cycle regulator CCND1, which in turn affects HCC tumorigenesis. Abbreviations: CCDN1: cyclin D1; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; SQSTM1: sequestosome 1.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Automated" Owner="NLM"><PMID Version="1">30646811</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>12</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>18</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1554-8635</ISSN><JournalIssue CitedMedium="Internet"><Volume>15</Volume><Issue>4</Issue><PubDate><Year>2019</Year><Month>04</Month></PubDate></JournalIssue><Title>Autophagy</Title><ISOAbbreviation>Autophagy</ISOAbbreviation></Journal><ArticleTitle>Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis.</ArticleTitle><Pagination><MedlinePgn>729-730</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/15548627.2019.1569918</ELocationID><Abstract><AbstractText>Overexpressed CCND1 (cyclin D1) is associated with hepatocellular carcinoma (HCC) and we used 147 tumor tissue samples from HCC patients and 3 murine models to reveal an inverse correlation between low autophagic activity and high CCND1 expression. These 2 phenomena in combination correlated with poor overall survival in HCC patients. Mechanistic analysis showed that activated autophagy triggered CCND1 ubiquitination followed by SQSTM1 (sequestosome 1)-mediated selective phagophore recruitment, autophagosome formation, fusion with a lysosome, and degradation. Functional studies revealed that autophagy-selective degradation of CCND1 suppresses DNA synthesis, cell proliferation, and colony, and liver tumor formation by arresting the cell cycle at the G<sub>1</sub> phase. Most importantly, diverse pharmacological inducers (rapamycin and amiodarone) effectively suppress tumor growth in orthotopic liver tumor and subcutaneous tumor xenograft models. In conclusion, we have demonstrated a link between degradative autophagy and the cell cycle regulator CCND1, and have discovered the underlying mechanism by which the autophagic degradation machinery regulates the turnover of the cell-cycle regulator CCND1, which in turn affects HCC tumorigenesis. Abbreviations: CCDN1: cyclin D1; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; SQSTM1: sequestosome 1.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Shan-Ying</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>a Department of Human Development and Family Studies , National Taiwan Normal University , Taipei , Taiwan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>b Department of Microbiology and Immunology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lan</LastName><ForeName>Sheng-Hui</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>c Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences , China Medical University , Taichung , Taiwan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Hsiao-Sheng</ForeName><Initials>HS</Initials><AffiliationInfo><Affiliation>b Department of Microbiology and Immunology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>d Institute of Basic Medical Sciences, College of Medicine , National Cheng Kung University , Tainan , Taiwan.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016420">Comment</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>01</Month><Day>31</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Autophagy</MedlineTA><NlmUniqueID>101265188</NlmUniqueID><ISSNLinking>1554-8627</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C530104">CCND1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C546140">MIRN224 microRNA, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D035683">MicroRNAs</NameOfSubstance></Chemical><Chemical><RegistryNumber>136601-57-5</RegistryNumber><NameOfSubstance UI="D019938">Cyclin D1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentOn"><RefSource>Hepatology. 2018 Jul;68(1):141-154</RefSource><PMID Version="1">29328502</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="Y">Autophagy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D063646" MajorTopicYN="N">Carcinogenesis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006528" MajorTopicYN="Y">Carcinoma, Hepatocellular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019938" MajorTopicYN="N">Cyclin D1</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008113" MajorTopicYN="Y">Liver Neoplasms</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D035683" MajorTopicYN="Y">MicroRNAs</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Autophagy</Keyword><Keyword MajorTopicYN="Y">CCND1</Keyword><Keyword MajorTopicYN="Y">HCC</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>1</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>1</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30646811</ArticleId><ArticleId IdType="doi">10.1080/15548627.2019.1569918</ArticleId><ArticleId IdType="pmc">PMC6526824</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Hepatology. 2018 Jul;68(1):141-154</Citation><ArticleIdList><ArticleId IdType="pubmed">29328502</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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