FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3081946688> ?p ?o ?g. }

• W3081946688 endingPage "3538" @default.
• W3081946688 startingPage "3523" @default.
• W3081946688 abstract "Abstract Pituitary adenomas (PAs) are intracranial tumors associated with significant morbidity due to hormonal dysregulation, mass effects and have a heavy treatment burden. Growth hormone (GH)‐secreting PAs (somatotropinomas) cause acromegaly‐gigantism. Genetic forms of somatotropinomas due to germline AIP mutations ( AIP mut+) have an early onset and are aggressive and resistant to treatment with somatostatin analogs (SSAs), including octreotide. The molecular underpinnings of these clinical features remain unclear. We investigated the role of miRNA dysregulation in AIP mut+ vs AIP mut− PA samples by array analysis. miR‐34a and miR‐145 were highly expressed in AIP mut+ vs AIP mut− somatotropinomas. Ectopic expression of AIP mut (p.R271W) in Aip −/− mouse embryonic fibroblasts (MEFs) upregulated miR‐34a and miR‐145, establishing a causal link between AIP mut and miRNA expression. In PA cells (GH3), miR‐34a overexpression promoted proliferation, clonogenicity, migration and suppressed apoptosis, whereas miR‐145 moderately affected proliferation and apoptosis. Moreover, high miR‐34a expression increased intracellular cAMP, a critical mitogenic factor in PAs. Crucially, high miR‐34a expression significantly blunted octreotide‐mediated GH inhibition and antiproliferative effects. miR‐34a directly targets Gnai2 encoding Gαi2, a G protein subunit inhibiting cAMP production. Accordingly, Gαi2 levels were significantly lower in AIP mut+ vs AIP mut− PA. Taken together, somatotropinomas with AIP mutations overexpress miR‐34a, which in turn downregulates Gαi2 expression, increases cAMP concentration and ultimately promotes cell growth. Upregulation of miR‐34a also impairs the hormonal and antiproliferative response of PA cells to octreotide. Thus, miR‐34a is a novel downstream target of mutant AIP that promotes a cellular phenotype mirroring the aggressive clinical features of AIP mut+ acromegaly." @default.
• W3081946688 created "2020-09-08" @default.
• W3081946688 creator A5001450937 @default.
• W3081946688 creator A5011100591 @default.
• W3081946688 creator A5013646231 @default.
• W3081946688 creator A5020890614 @default.
• W3081946688 creator A5037139423 @default.
• W3081946688 creator A5066308890 @default.
• W3081946688 creator A5073200002 @default.
• W3081946688 creator A5090438911 @default.
• W3081946688 creator A5091051936 @default.
• W3081946688 date "2020-09-10" @default.
• W3081946688 modified "2023-10-18" @default.
• W3081946688 title "<scp>miR</scp> ‐34a is upregulated in <i> <scp>AIP</scp> ‐ </i> mutated somatotropinomas and promotes octreotide resistance" @default.
• W3081946688 cites W1511075797 @default.
• W3081946688 cites W1543035538 @default.
• W3081946688 cites W1963776701 @default.
• W3081946688 cites W1969529910 @default.
• W3081946688 cites W1973023724 @default.
• W3081946688 cites W1973902556 @default.
• W3081946688 cites W1974366727 @default.
• W3081946688 cites W1977376661 @default.
• W3081946688 cites W1981960074 @default.
• W3081946688 cites W1987488732 @default.
• W3081946688 cites W1993095991 @default.
• W3081946688 cites W1995339870 @default.
• W3081946688 cites W1998095188 @default.
• W3081946688 cites W2009350817 @default.
• W3081946688 cites W2010375889 @default.
• W3081946688 cites W2014943797 @default.
• W3081946688 cites W2019236236 @default.
• W3081946688 cites W2021533793 @default.
• W3081946688 cites W2030150930 @default.
• W3081946688 cites W2030863497 @default.
• W3081946688 cites W2035630269 @default.
• W3081946688 cites W2045374621 @default.
• W3081946688 cites W2066636886 @default.
• W3081946688 cites W2074430966 @default.
• W3081946688 cites W2074882915 @default.
• W3081946688 cites W2102705825 @default.
• W3081946688 cites W2105697797 @default.
• W3081946688 cites W2107607858 @default.
• W3081946688 cites W2110273815 @default.
• W3081946688 cites W2115325231 @default.
• W3081946688 cites W2121563344 @default.
• W3081946688 cites W2126504105 @default.
• W3081946688 cites W2132094049 @default.
• W3081946688 cites W2143755574 @default.
• W3081946688 cites W2152147743 @default.
• W3081946688 cites W2155465275 @default.
• W3081946688 cites W2156543203 @default.
• W3081946688 cites W2158288324 @default.
• W3081946688 cites W2159724161 @default.
• W3081946688 cites W2172579382 @default.
• W3081946688 cites W2255429993 @default.
• W3081946688 cites W2331963725 @default.
• W3081946688 cites W2415653838 @default.
• W3081946688 cites W2417241808 @default.
• W3081946688 cites W2427851148 @default.
• W3081946688 cites W2532860295 @default.
• W3081946688 cites W2562628519 @default.
• W3081946688 cites W2564278427 @default.
• W3081946688 cites W2569852888 @default.
• W3081946688 cites W2571305185 @default.
• W3081946688 cites W2596640287 @default.
• W3081946688 cites W2750649250 @default.
• W3081946688 cites W2799981599 @default.
• W3081946688 cites W2827296137 @default.
• W3081946688 cites W2898236455 @default.
• W3081946688 cites W2913505551 @default.
• W3081946688 cites W2918786855 @default.
• W3081946688 cites W2945507083 @default.
• W3081946688 cites W2948512019 @default.
• W3081946688 cites W4234865248 @default.
• W3081946688 doi "https://doi.org/10.1002/ijc.33268" @default.
• W3081946688 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32856736" @default.
• W3081946688 hasPublicationYear "2020" @default.
• W3081946688 type Work @default.
• W3081946688 sameAs 3081946688 @default.
• W3081946688 citedByCount "21" @default.
• W3081946688 countsByYear W30819466882021 @default.
• W3081946688 countsByYear W30819466882022 @default.
• W3081946688 countsByYear W30819466882023 @default.
• W3081946688 crossrefType "journal-article" @default.
• W3081946688 hasAuthorship W3081946688A5001450937 @default.
• W3081946688 hasAuthorship W3081946688A5011100591 @default.
• W3081946688 hasAuthorship W3081946688A5013646231 @default.
• W3081946688 hasAuthorship W3081946688A5020890614 @default.
• W3081946688 hasAuthorship W3081946688A5037139423 @default.
• W3081946688 hasAuthorship W3081946688A5066308890 @default.
• W3081946688 hasAuthorship W3081946688A5073200002 @default.
• W3081946688 hasAuthorship W3081946688A5090438911 @default.
• W3081946688 hasAuthorship W3081946688A5091051936 @default.
• W3081946688 hasBestOaLocation W30819466881 @default.
• W3081946688 hasConcept C104317684 @default.
• W3081946688 hasConcept C126322002 @default.
• W3081946688 hasConcept C127561419 @default.
• W3081946688 hasConcept C134018914 @default.

• next