FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2117852569> ?p ?o ?g. }

• W2117852569 abstract "Glioblastoma (GBM) is the most common primary brain malignancy and confers a dismal prognosis. GBMs harbor glioblastoma-initiating cells (GICs) that drive tumorigenesis and contribute to therapeutic resistance and tumor recurrence. Consequently, there is a strong rationale to target this cell population in order to develop new molecular therapies against GBM. Accumulating evidence indicates that Nα-terminal acetyltransferases (NATs), that are dysregulated in numerous human cancers, can serve as therapeutic targets. Microarrays were used to study the expression of several NATs including NAT12/NAA30 in clinical samples and stem cell cultures. The expression of NAT12/NAA30 was analyzed using qPCR, immunolabeling and western blot. We conducted shRNA-mediated knockdown of NAT12/NAA30 gene in GICs and studied the effects on cell viability, sphere-formation and hypoxia sensitivity. Intracranial transplantation to SCID mice enabled us to investigate the effects of NAT12/NAA30 depletion in vivo. Using microarrays we identified genes and biochemical pathways whose expression was altered upon NAT12/NAA30 down-regulation. While decreased expression of the distal 3’UTR of NAT12/NAA30 was generally observed in GICs and GBMs, this gene was strongly up-regulated at the protein level in GBM and GICs. The increased protein levels were not caused by increased levels of the steady state mRNA but rather by other mechanisms. Also, shorter 3’UTR of NAT12/NAA30 correlated with poor survival in glioma patients. As well, we observed previously not described nuclear localization of this typically cytoplasmic protein. When compared to non-silencing controls, cells featuring NAT12/NAA30 knockdown exhibited reduced cell viability, sphere-forming ability, and mitochondrial hypoxia tolerance. Intracranial transplantation showed that knockdown of NAT12/NAA30 resulted in prolonged animal survival. Microarray analysis of the knockdown cultures showed reduced levels of HIF1α and altered expression of several other genes involved in the hypoxia response. Furthermore, NAT12/NAA30 knockdown correlated with expressional dysregulation of genes involved in the p53 pathway, ribosomal assembly and cell proliferation. Western blot analysis revealed reduction of HIF1α, phospho-MTOR(Ser2448) and higher levels of p53 and GFAP in these cultures. NAT12/NAA30 plays an important role in growth and survival of GICs possibly by regulating hypoxia response (HIF1α), levels of p-MTOR (Ser2448) and the p53 pathway." @default.
• W2117852569 created "2016-06-24" @default.
• W2117852569 creator A5006360278 @default.
• W2117852569 creator A5018599880 @default.
• W2117852569 creator A5021592085 @default.
• W2117852569 creator A5032646778 @default.
• W2117852569 creator A5039225238 @default.
• W2117852569 creator A5044030005 @default.
• W2117852569 creator A5048023071 @default.
• W2117852569 creator A5054415263 @default.
• W2117852569 creator A5081549003 @default.
• W2117852569 creator A5091101546 @default.
• W2117852569 creator A5091284297 @default.
• W2117852569 date "2015-08-21" @default.
• W2117852569 modified "2023-10-17" @default.
• W2117852569 title "Knockdown of NAT12/NAA30 reduces tumorigenic features of glioblastoma-initiating cells" @default.
• W2117852569 cites W141311245 @default.
• W2117852569 cites W1456958198 @default.
• W2117852569 cites W1506994362 @default.
• W2117852569 cites W1526449859 @default.
• W2117852569 cites W1823890220 @default.
• W2117852569 cites W1966411411 @default.
• W2117852569 cites W1967403316 @default.
• W2117852569 cites W1971046933 @default.
• W2117852569 cites W1989360500 @default.
• W2117852569 cites W1994901446 @default.
• W2117852569 cites W1998542618 @default.
• W2117852569 cites W1999601388 @default.
• W2117852569 cites W2006897037 @default.
• W2117852569 cites W2008206202 @default.
• W2117852569 cites W2010081999 @default.
• W2117852569 cites W2015675870 @default.
• W2117852569 cites W2018671779 @default.
• W2117852569 cites W2033192575 @default.
• W2117852569 cites W2033750217 @default.
• W2117852569 cites W2036412428 @default.
• W2117852569 cites W2039075677 @default.
• W2117852569 cites W2039947540 @default.
• W2117852569 cites W2044805507 @default.
• W2117852569 cites W2048492672 @default.
• W2117852569 cites W2052110007 @default.
• W2117852569 cites W2058544861 @default.
• W2117852569 cites W2060551076 @default.
• W2117852569 cites W2064012961 @default.
• W2117852569 cites W2064723275 @default.
• W2117852569 cites W2070329840 @default.
• W2117852569 cites W2072080280 @default.
• W2117852569 cites W2073817956 @default.
• W2117852569 cites W2078510083 @default.
• W2117852569 cites W2080100938 @default.
• W2117852569 cites W2083081144 @default.
• W2117852569 cites W2087214667 @default.
• W2117852569 cites W2088195663 @default.
• W2117852569 cites W2090395289 @default.
• W2117852569 cites W2097985443 @default.
• W2117852569 cites W2099249565 @default.
• W2117852569 cites W2099463987 @default.
• W2117852569 cites W2099915768 @default.
• W2117852569 cites W2100004531 @default.
• W2117852569 cites W2104427376 @default.
• W2117852569 cites W2123285201 @default.
• W2117852569 cites W2124078079 @default.
• W2117852569 cites W2127307105 @default.
• W2117852569 cites W2128064256 @default.
• W2117852569 cites W2133465414 @default.
• W2117852569 cites W2141174309 @default.
• W2117852569 cites W2143348980 @default.
• W2117852569 cites W2146369144 @default.
• W2117852569 cites W2148977460 @default.
• W2117852569 cites W2157388625 @default.
• W2117852569 cites W2158217645 @default.
• W2117852569 cites W2164083634 @default.
• W2117852569 cites W2164095335 @default.
• W2117852569 cites W2167414381 @default.
• W2117852569 cites W2167650288 @default.
• W2117852569 cites W2168414172 @default.
• W2117852569 cites W2169392156 @default.
• W2117852569 cites W2391415472 @default.
• W2117852569 cites W4293529598 @default.
• W2117852569 doi "https://doi.org/10.1186/s12943-015-0432-z" @default.
• W2117852569 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4546247" @default.
• W2117852569 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26292663" @default.
• W2117852569 hasPublicationYear "2015" @default.
• W2117852569 type Work @default.
• W2117852569 sameAs 2117852569 @default.
• W2117852569 citedByCount "28" @default.
• W2117852569 countsByYear W21178525692016 @default.
• W2117852569 countsByYear W21178525692017 @default.
• W2117852569 countsByYear W21178525692018 @default.
• W2117852569 countsByYear W21178525692019 @default.
• W2117852569 countsByYear W21178525692020 @default.
• W2117852569 countsByYear W21178525692021 @default.
• W2117852569 countsByYear W21178525692022 @default.
• W2117852569 countsByYear W21178525692023 @default.
• W2117852569 crossrefType "journal-article" @default.
• W2117852569 hasAuthorship W2117852569A5006360278 @default.
• W2117852569 hasAuthorship W2117852569A5018599880 @default.
• W2117852569 hasAuthorship W2117852569A5021592085 @default.
• W2117852569 hasAuthorship W2117852569A5032646778 @default.
• W2117852569 hasAuthorship W2117852569A5039225238 @default.

• next