Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features.
pituitary neuroendocrine tumors
pladienolide-B.
spliceosome
splicing
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
26 09 2019
26 09 2019
Historique:
received:
02
08
2019
revised:
09
09
2019
accepted:
23
09
2019
entrez:
29
9
2019
pubmed:
29
9
2019
medline:
29
9
2019
Statut:
epublish
Résumé
Pituitary neuroendocrine tumors (PitNETs) constitute approximately 15% of all brain tumors, and most have a sporadic origin. Recent studies suggest that altered alternative splicing and, consequently, appearance of aberrant splicing variants, is a common feature of most tumor pathologies. Moreover, spliceosome is considered an attractive therapeutic target in tumor pathologies, and the inhibition of SF3B1 (e.g., using pladienolide-B) has been shown to exert antitumor effects. Therefore, we aimed to analyze the expression levels of selected splicing-machinery components in 261 PitNETs (somatotropinomas/non-functioning PitNETS/corticotropinomas/prolactinomas) and evaluated the direct effects of pladienolide-B in cell proliferation/viability/hormone secretion in human PitNETs cell cultures and pituitary cell lines (AtT-20/GH3). Results revealed a severe dysregulation of splicing-machinery components in all the PitNET subtypes compared to normal pituitaries and a unique fingerprint of splicing-machinery components that accurately discriminate between normal and tumor tissue in each PitNET subtype. Moreover, expression of specific components was associated with key clinical parameters. Interestingly, certain components were commonly dysregulated throughout all PitNET subtypes. Finally, pladienolide-B reduced cell proliferation/viability/hormone secretion in PitNET cell cultures and cell lines. Altogether, our data demonstrate a drastic dysregulation of the splicing-machinery in PitNETs that might be associated to their tumorigenesis, paving the way to explore the use of specific splicing-machinery components as novel diagnostic/prognostic and therapeutic targets in PitNETs.
Identifiants
pubmed: 31561558
pii: cancers11101439
doi: 10.3390/cancers11101439
pmc: PMC6826715
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Junta de Andalucía
ID : CTS-1406
Pays : International
Organisme : Junta de Andalucía
ID : BIO-0139
Pays : International
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : BFU2016-80360-R
Pays : International
Organisme : Instituto de Salud Carlos III
ID : PI16/00264
Pays : International
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
PLoS One. 2017 Aug 11;12(8):e0182512
pubmed: 28800641
Endocrine. 2015 Nov;50(2):442-52
pubmed: 25854304
FASEB J. 2017 Nov;31(11):4682-4696
pubmed: 28705809
Oncol Lett. 2018 Apr;15(4):4745-4752
pubmed: 29552114
Nat Rev Mol Cell Biol. 2013 Mar;14(3):153-65
pubmed: 23385723
Nat Rev Endocrinol. 2011 May;7(5):257-66
pubmed: 21423242
EMBO Rep. 2015 Dec;16(12):1640-55
pubmed: 26566663
Endokrynol Pol. 2016;67(3):292-8
pubmed: 27345147
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
pubmed: 12184808
Oncotarget. 2016 Feb 9;7(6):6593-608
pubmed: 26673010
PLoS Genet. 2017 Mar 6;13(3):e1006589
pubmed: 28263985
Neuro Oncol. 2019 Jun 10;21(6):742-754
pubmed: 30753603
Oncol Rep. 2006 May;15(5):1249-56
pubmed: 16596194
Oncogene. 2016 May 12;35(19):2413-27
pubmed: 26300000
Oncotarget. 2015 Aug 14;6(23):19619-33
pubmed: 26124083
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3389-3402
pubmed: 30901032
Sci Rep. 2017 Feb 09;7:42002
pubmed: 28181484
Nat Cell Biol. 2019 May;21(5):640-650
pubmed: 31011167
JAMA. 2017 Feb 7;317(5):516-524
pubmed: 28170483
Nature. 1992 Sep 24;359(6393):295-300
pubmed: 1406933
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3501-3513
pubmed: 30860580
Curr Protoc Bioinformatics. 2016 Sep 07;55:14.10.1-14.10.91
pubmed: 27603023
Oncotarget. 2016 Sep 13;7(37):60110-60122
pubmed: 27507050
Oncogene. 2012 Apr 19;31(16):2049-61
pubmed: 21927030
PLoS One. 2017 Feb 13;12(2):e0172209
pubmed: 28192473
EBioMedicine. 2018 Nov;37:356-365
pubmed: 30446432
Nat Med. 2016 Sep 7;22(9):976-86
pubmed: 27603132
Cancer Lett. 2015 Apr 10;359(2):299-306
pubmed: 25637790
Sci Rep. 2015 Mar 04;5:8714
pubmed: 25737012
J Clin Endocrinol Metab. 2013 Oct;98(10):4160-9
pubmed: 23884782
Ann N Y Acad Sci. 2018 Dec;1433(1):53-60
pubmed: 30216461
Oncogene. 2019 Jul;38(27):5381-5395
pubmed: 30867568
BMC Cancer. 2018 Nov 12;18(1):1106
pubmed: 30419865
EMBO Mol Med. 2013 May;5(5):737-50
pubmed: 23592547
Plant Mol Biol. 2012 Jan 31;:null
pubmed: 22290409
Med Sci Monit. 2016 Sep 13;22:3248-56
pubmed: 27623016
Pituitary. 2018 Apr;21(2):130-137
pubmed: 29404893
Methods Mol Biol. 2013;946:1-13
pubmed: 23179822
Cell Res. 2016 Nov;26(11):1255-1259
pubmed: 27670697
Transl Res. 2019 Oct;212:89-103
pubmed: 31344348
Mol Cancer Res. 2014 Sep;12(9):1195-204
pubmed: 24807918
J Endocrinol. 2016 Nov;231(2):135-145
pubmed: 27587848
Endocr Pathol. 2017 Sep;28(3):228-243
pubmed: 28766057
Clin Cancer Res. 2018 Sep 1;24(17):4126-4136
pubmed: 30084836
Endocr Relat Cancer. 2015 Feb;22(1):111-9
pubmed: 25515731
RNA Biol. 2018;15(10):1364-1375
pubmed: 30321081
J Breast Cancer. 2018 Sep;21(3):288-296
pubmed: 30275857
Theranostics. 2019 Jan 1;9(1):179-195
pubmed: 30662561
Clin Cancer Res. 2016 Oct 15;22(20):5030-5042
pubmed: 27742789
Mol Cells. 2018 Aug 31;41(8):733-741
pubmed: 29991672
Clin Endocrinol (Oxf). 2007 Mar;66(3):348-52
pubmed: 17302867
Genome Biol. 2014 Jan 31;15(1):R20
pubmed: 24485098
Mol Cancer. 2017 Aug 29;16(1):146
pubmed: 28851363
Nature. 2013 May 2;497(7447):127-31
pubmed: 23615609
Biochem Biophys Res Commun. 2012 Jan 6;417(1):588-93
pubmed: 22178073
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1273-1280
pubmed: 30963795
J Cancer Res Clin Oncol. 2019 Apr;145(4):873-879
pubmed: 30758670
J Mol Endocrinol. 2010 Feb;44(2):127-34
pubmed: 19897610
Br J Cancer. 2009 Jan 27;100(2):228-32
pubmed: 19034274
Biochem Biophys Res Commun. 2006 Feb 17;340(3):995-1005
pubmed: 16403460
Cold Spring Harb Perspect Biol. 2019 Jan 2;11(1):
pubmed: 30602541
Endocr Relat Cancer. 2017 Apr;24(4):C5-C8
pubmed: 28264912
J Clin Endocrinol Metab. 2009 Jul;94(7):2634-43
pubmed: 19401364
PLoS One. 2014 Jan 21;9(1):e85527
pubmed: 24465589
Cell. 1996 May 31;85(5):721-32
pubmed: 8646780
Haematologica. 2015 Jul;100(7):945-54
pubmed: 25862704
J Clin Endocrinol Metab. 2009 Jun;94(6):1931-7
pubmed: 19293270
Prostate. 2019 Jan;79(1):96-104
pubmed: 30155992
Neuro Endocrinol Lett. 2015;36(2):136-42
pubmed: 26071582
Sci Rep. 2019 May 20;9(1):7618
pubmed: 31110284
J Clin Endocrinol Metab. 2013 Nov;98(11):E1730-9
pubmed: 24092823
Trends Biochem Sci. 2012 May;37(5):179-88
pubmed: 22480731
Endocr Relat Cancer. 2015 Jun;22(3):353-67
pubmed: 25712922
BMC Med Genomics. 2014 Dec 24;7:69
pubmed: 25539738
FEBS J. 2011 Dec;278(24):4870-80
pubmed: 21981285
J Cell Biol. 1999 Jun 28;145(7):1355-68
pubmed: 10385517
Biochemistry. 2017 Sep 12;56(36):4757-4761
pubmed: 28850223
Nat Rev Mol Cell Biol. 2009 Nov;10(11):741-54
pubmed: 19773805
Cancer Sci. 2014 Jan;105(1):110-6
pubmed: 24635824
Eur J Endocrinol. 2007 Jan;156(1):65-74
pubmed: 17218727
Clin Cancer Res. 2017 Apr 1;23(7):1841-1851
pubmed: 27707790