Long Noncoding RNA CUDR Regulates HULC and β-Catenin to Govern Human Liver Stem Cell Malignant Differentiation

Long noncoding RNA cancer upregulated drug resistant (CUDR) is overexpressed in many tumors and promotes tumorigenesis. Herein, we demonstrate CUDR could enhance the human embryonic stem cells (ESC) differentiation into hepatocyte-like cells by reducing trimethylation on histone H3 twenty-seventh ly...

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Published in:Molecular therapy 2015-12, Vol.23 (12), p.1843-1853
Main Authors: Gui, Xin, Li, Haiyan, Li, Tianming, Pu, Hu, Lu, Dongdong
Format: Article
Language:English
Subjects:
beta Catenin - genetics
beta Catenin - metabolism
CCCTC-Binding Factor
Cell Differentiation
Cell Line, Tumor
Cell Transformation, Neoplastic - genetics
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Gene Expression Regulation, Neoplastic
Hepatocytes - cytology
Hepatocytes - metabolism
Histones - genetics
Histones - metabolism
Humans
Liver - cytology
Liver - metabolism
Liver Neoplasms - therapy
Original
Promoter Regions, Genetic
Repressor Proteins - genetics
Repressor Proteins - metabolism
RNA, Long Noncoding - genetics
Signal Transduction
Up-Regulation
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cited_by cdi_FETCH-LOGICAL-c530t-cda07633e3de9e03d8f589bea69787c280bdad16a15b47be85eb8327ddafaf5e3
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container_issue 12
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container_title Molecular therapy
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creator Gui, Xin
Li, Haiyan
Li, Tianming
Pu, Hu
Lu, Dongdong
description Long noncoding RNA cancer upregulated drug resistant (CUDR) is overexpressed in many tumors and promotes tumorigenesis. Herein, we demonstrate CUDR could enhance the human embryonic stem cells (ESC) differentiation into hepatocyte-like cells by reducing trimethylation on histone H3 twenty-seventh lysine (H3K27me3). On the other hand, excessive CUDR triggers hepatocyte-like cells malignant transformation. Mechanistically, we identify CUDR causes highly upregulated in liver cancer (HULC) and β-catenin abnormal expression by inhibiting HULC promoter methylation and promoting β-catenin promoter-enhancer chromatin looping formation mediated by CUDR-ccctc-binding factor (CTCF) complex, which recruits more RNA polII and P300. Strikingly, HULC and β-catenin activity are crucial for CUDR oncogenic function. These findings provide the first demonstration that CUDR plays a positive potential role in liver cancer stem cell through the cascade of CUDR-HULC/CUDR-β-catenin signaling, and offer insights into a novel link between long noncoding RNA (lncRNA) and the epigenetic modification in cancer stem cells.
doi_str_mv 10.1038/mt.2015.166
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These findings provide the first demonstration that CUDR plays a positive potential role in liver cancer stem cell through the cascade of CUDR-HULC/CUDR-β-catenin signaling, and offer insights into a novel link between long noncoding RNA (lncRNA) and the epigenetic modification in cancer stem cells.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1038/mt.2015.166</identifier><identifier>PMID: 26347501</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>beta Catenin - genetics ; beta Catenin - metabolism ; CCCTC-Binding Factor ; Cell Differentiation ; Cell Line, Tumor ; Cell Transformation, Neoplastic - genetics ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Gene Expression Regulation, Neoplastic ; Hepatocytes - cytology ; Hepatocytes - metabolism ; Histones - genetics ; Histones - metabolism ; Humans ; Liver - cytology ; Liver - metabolism ; Liver Neoplasms - therapy ; Original ; Promoter Regions, Genetic ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; RNA, Long Noncoding - genetics ; Signal Transduction ; Up-Regulation</subject><ispartof>Molecular therapy, 2015-12, Vol.23 (12), p.1843-1853</ispartof><rights>2015 American Society of Gene &amp; Cell Therapy</rights><rights>Copyright © 2015 American Society of Gene &amp; Cell Therapy 2015 American Society of Gene &amp; Cell Therapy</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-cda07633e3de9e03d8f589bea69787c280bdad16a15b47be85eb8327ddafaf5e3</citedby><cites>FETCH-LOGICAL-c530t-cda07633e3de9e03d8f589bea69787c280bdad16a15b47be85eb8327ddafaf5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700108/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700108/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26347501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gui, Xin</creatorcontrib><creatorcontrib>Li, Haiyan</creatorcontrib><creatorcontrib>Li, Tianming</creatorcontrib><creatorcontrib>Pu, Hu</creatorcontrib><creatorcontrib>Lu, Dongdong</creatorcontrib><title>Long Noncoding RNA CUDR Regulates HULC and β-Catenin to Govern Human Liver Stem Cell Malignant Differentiation</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Long noncoding RNA cancer upregulated drug resistant (CUDR) is overexpressed in many tumors and promotes tumorigenesis. 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subjects beta Catenin - genetics
beta Catenin - metabolism
CCCTC-Binding Factor
Cell Differentiation
Cell Line, Tumor
Cell Transformation, Neoplastic - genetics
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Gene Expression Regulation, Neoplastic
Hepatocytes - cytology
Hepatocytes - metabolism
Histones - genetics
Histones - metabolism
Humans
Liver - cytology
Liver - metabolism
Liver Neoplasms - therapy
Original
Promoter Regions, Genetic
Repressor Proteins - genetics
Repressor Proteins - metabolism
RNA, Long Noncoding - genetics
Signal Transduction
Up-Regulation
title Long Noncoding RNA CUDR Regulates HULC and β-Catenin to Govern Human Liver Stem Cell Malignant Differentiation
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