Matches in SemOpenAlex for { <https://semopenalex.org/work/W2883225927> ?p ?o ?g. }
- W2883225927 endingPage "1563" @default.
- W2883225927 startingPage "1549" @default.
- W2883225927 abstract "Functions of transforming growth factor‐β (TGF‐β) in the liver vary depending on specific cell types and their temporal response to TGF‐β during different stages of hepatocarcinogenesis (HCG). Through analysis of tumor tissues from hepatocellular carcinoma (HCC) patients, we were able to cluster hepatic epithelial cell‐derived TGF‐β gene signatures in association with distinct clinical prognoses. To delineate the role of hepatic epithelial TGF‐β signaling in HCC development, we used an experimental system in which tumor‐initiating hepatocytes (TICs) were isolated from TGF‐β receptor II floxed mice ( Tgfbr2fl/fl ) and transplanted into syngeneic C57BL/6J mice by splenic injection. Recipient mice were then administered Cre‐expressing adenovirus (Ad‐Cre) to inactivate Tgfbr2 in transplanted TICs. After latency, Tgfbr2‐inactivated TICs formed larger and more tumor nodules in recipient livers compared to TICs without Tgfbr2 inactivation. In vitro analyses revealed that treatment of cultured TICs with TGF‐β inhibited expression of progenitor cell factors (including SRY (sex determining region Y)‐box 2 [Sox2]). RNA sequencing (RNA‐seq) analysis identified H19 as one of the most up‐regulated long noncoding RNA (lncRNA) in association with Tgfbr2 inactivation in TICs. Tgfbr2 inactivation by Ad‐Cre led to a 5‐fold increase of H19 expression in TICs. Accordingly, TGF‐β treatment reduced H19 expression. We observed that forced overexpression of Sox2 in TICs increased transcription of H19, whereas knockdown of Sox2 decreased it. Furthermore, depletion of H19 reduced the progenitor property of TICs in vitro and decreased their tumorigenic potential in vivo . Finally, we observed a low level of H19 mRNA expression in human HCC tissues from patients with the epithelial TGF‐β gene signature in association with favorable prognosis. Conclusion: Our findings describe a TGF‐β and H19 signaling axis by Sox2 in TICs that importantly regulates HCG." @default.
- W2883225927 created "2018-08-03" @default.
- W2883225927 creator A5006415081 @default.
- W2883225927 creator A5012895760 @default.
- W2883225927 creator A5018863416 @default.
- W2883225927 creator A5041192749 @default.
- W2883225927 creator A5051751803 @default.
- W2883225927 creator A5051779747 @default.
- W2883225927 creator A5055563614 @default.
- W2883225927 creator A5083305672 @default.
- W2883225927 creator A5091718131 @default.
- W2883225927 date "2018-12-31" @default.
- W2883225927 modified "2023-09-22" @default.
- W2883225927 title "A Transforming Growth Factor‐β and H19 Signaling Axis in Tumor‐Initiating Hepatocytes That Regulates Hepatic Carcinogenesis" @default.
- W2883225927 cites W1589755113 @default.
- W2883225927 cites W1658496141 @default.
- W2883225927 cites W1820504382 @default.
- W2883225927 cites W1963920328 @default.
- W2883225927 cites W1970098795 @default.
- W2883225927 cites W1972050299 @default.
- W2883225927 cites W1974724756 @default.
- W2883225927 cites W1976794059 @default.
- W2883225927 cites W1987361483 @default.
- W2883225927 cites W1990376085 @default.
- W2883225927 cites W1991098379 @default.
- W2883225927 cites W1995940697 @default.
- W2883225927 cites W2010890262 @default.
- W2883225927 cites W2011821756 @default.
- W2883225927 cites W2019242560 @default.
- W2883225927 cites W2052656103 @default.
- W2883225927 cites W2056671120 @default.
- W2883225927 cites W2058068487 @default.
- W2883225927 cites W2060606699 @default.
- W2883225927 cites W2070067278 @default.
- W2883225927 cites W2073161725 @default.
- W2883225927 cites W2081290563 @default.
- W2883225927 cites W2082401103 @default.
- W2883225927 cites W2083549154 @default.
- W2883225927 cites W2085114559 @default.
- W2883225927 cites W2088629624 @default.
- W2883225927 cites W2091669222 @default.
- W2883225927 cites W2093404711 @default.
- W2883225927 cites W2094751839 @default.
- W2883225927 cites W2101378959 @default.
- W2883225927 cites W2107144403 @default.
- W2883225927 cites W2123927899 @default.
- W2883225927 cites W2129680066 @default.
- W2883225927 cites W2130543801 @default.
- W2883225927 cites W2140586060 @default.
- W2883225927 cites W2145357082 @default.
- W2883225927 cites W2151220680 @default.
- W2883225927 cites W2167583762 @default.
- W2883225927 cites W2168089202 @default.
- W2883225927 cites W2173273606 @default.
- W2883225927 cites W2173632235 @default.
- W2883225927 cites W2235152311 @default.
- W2883225927 cites W2256023856 @default.
- W2883225927 cites W2280923709 @default.
- W2883225927 cites W2334552535 @default.
- W2883225927 cites W2426080969 @default.
- W2883225927 cites W2520301334 @default.
- W2883225927 cites W2585223803 @default.
- W2883225927 doi "https://doi.org/10.1002/hep.30153" @default.
- W2883225927 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6335184" @default.
- W2883225927 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30014520" @default.
- W2883225927 hasPublicationYear "2018" @default.
- W2883225927 type Work @default.
- W2883225927 sameAs 2883225927 @default.
- W2883225927 citedByCount "52" @default.
- W2883225927 countsByYear W28832259272018 @default.
- W2883225927 countsByYear W28832259272019 @default.
- W2883225927 countsByYear W28832259272020 @default.
- W2883225927 countsByYear W28832259272021 @default.
- W2883225927 countsByYear W28832259272022 @default.
- W2883225927 countsByYear W28832259272023 @default.
- W2883225927 crossrefType "journal-article" @default.
- W2883225927 hasAuthorship W2883225927A5006415081 @default.
- W2883225927 hasAuthorship W2883225927A5012895760 @default.
- W2883225927 hasAuthorship W2883225927A5018863416 @default.
- W2883225927 hasAuthorship W2883225927A5041192749 @default.
- W2883225927 hasAuthorship W2883225927A5051751803 @default.
- W2883225927 hasAuthorship W2883225927A5051779747 @default.
- W2883225927 hasAuthorship W2883225927A5055563614 @default.
- W2883225927 hasAuthorship W2883225927A5083305672 @default.
- W2883225927 hasAuthorship W2883225927A5091718131 @default.
- W2883225927 hasBestOaLocation W28832259272 @default.
- W2883225927 hasConcept C104317684 @default.
- W2883225927 hasConcept C118131993 @default.
- W2883225927 hasConcept C126322002 @default.
- W2883225927 hasConcept C134018914 @default.
- W2883225927 hasConcept C153911025 @default.
- W2883225927 hasConcept C173396325 @default.
- W2883225927 hasConcept C201750760 @default.
- W2883225927 hasConcept C2777933648 @default.
- W2883225927 hasConcept C28328180 @default.
- W2883225927 hasConcept C502942594 @default.
- W2883225927 hasConcept C54355233 @default.
- W2883225927 hasConcept C55493867 @default.