RNA-binding protein NONO promotes breast cancer proliferation by post-transcriptional regulation of SKP2 and E2F8.
Breast Neoplasms
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
DNA-Binding Proteins
/ genetics
Female
Gene Expression Regulation
/ genetics
Humans
Immunoprecipitation
/ methods
MCF-7 Cells
RNA Processing, Post-Transcriptional
/ genetics
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ genetics
Repressor Proteins
/ genetics
S-Phase Kinase-Associated Proteins
/ genetics
NONO
RNA-binding protein
breast cancer
post-transcriptional regulation
splicing
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
16
08
2019
revised:
19
10
2019
accepted:
05
11
2019
pubmed:
17
11
2019
medline:
14
1
2020
entrez:
17
11
2019
Statut:
ppublish
Résumé
The majority of breast cancers are primarily hormone-sensitive and can be managed by endocrine therapy, although therapy-resistant or hormone-refractory cancers need alternative treatments. Recently, increasing attention is being paid to RNA-binding proteins (RBP) in cancer pathophysiology. The precise role of RBP in breast cancer, however, remains to be clarified. We herein show that an RBP non-POU domain-containing octamer binding (NONO) plays a critical role in the pathophysiology of breast cancers regardless of their hormone dependency. Clinicopathological and immunohistochemical study of 127 breast cancer cases showed that NONO is a significant independent prognostic factor for breast cancer patients. Notably, siRNA-mediated NONO knockdown substantially repressed the proliferation of both hormone-sensitive MCF-7 and hormone-refractory MB-MDA-231 breast cancer cells. Integrative analysis combined with expression microarray and RIP-sequencing (RNA immunoprecipitation-sequencing) showed that NONO post-transcriptionally regulates the expression of cell proliferation-related genes by binding to their mRNAs, as exemplified by S-phase-associated kinase 2 and E2F transcription factor 8. Overall, these results suggest that NONO is a key regulator for breast cancer proliferation through the pre-mRNA splicing of cell proliferation-related genes and could be a potential new diagnostic and therapeutic target for advanced disease.
Identifiants
pubmed: 31733123
doi: 10.1111/cas.14240
pmc: PMC6942431
doi:
Substances chimiques
DNA-Binding Proteins
0
E2F8 protein, human
0
NONO protein, human
0
RNA, Messenger
0
RNA-Binding Proteins
0
Repressor Proteins
0
S-Phase Kinase-Associated Proteins
0
SKP2 protein, human
0
Banques de données
GENBANK
['GSE132742', 'GSE132743', 'GSE133423']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
148-159Subventions
Organisme : Strategic Research Center in Private Universities
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 15K15353
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 16K09809
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 17H04205
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 17K18061
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 18J00252
Organisme : Takeda Science Foundation
Organisme : Practical Research for Innovative Cancer Control
ID : JP18ck0106194
Organisme : Project for Cancer Research and Therapeutic Evolution
ID : P-CREATE
Organisme : Project for Cancer Research and Therapeutic Evolution
ID : JP18cm0106144
Informations de copyright
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
PLoS One. 2018 Dec 26;13(12):e0208351
pubmed: 30586414
Nat Commun. 2016 May 10;7:11479
pubmed: 27161491
Front Biosci (Elite Ed). 2015 Jan 01;7:1-41
pubmed: 25553361
Ecancermedicalscience. 2019 Jan 15;13:891
pubmed: 30792808
Mol Med. 2017 Jun;23:101-111
pubmed: 28474731
Nucleic Acids Res. 2016 May 19;44(9):3989-4004
pubmed: 27084935
Cell. 2013 Aug 1;154(3):556-68
pubmed: 23911321
Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):
pubmed: 21047916
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Cancer Sci. 2020 Jan;111(1):148-159
pubmed: 31733123
Asian Pac J Cancer Prev. 2016;17(S3):43-6
pubmed: 27165206
Curr Biol. 2002 Jan 8;12(1):13-25
pubmed: 11790299
Cell Rep. 2018 Mar 20;22(12):3191-3205
pubmed: 29562176
Oncotarget. 2016 Apr 26;7(17):23757-71
pubmed: 26992224
Int J Mol Sci. 2017 Sep 08;18(9):
pubmed: 28885545
Nature. 2013 Jul 11;499(7457):172-7
pubmed: 23846655
Breast Cancer Res Treat. 2010 Oct;123(3):725-31
pubmed: 20020197
Annu Rev Med. 2011;62:233-47
pubmed: 20887199
J Clin Endocrinol Metab. 2005 Aug;90(8):4671-8
pubmed: 15914529
Oncogene. 2016 Mar 17;35(11):1399-410
pubmed: 26148231
Bioinformatics. 2012 Dec 1;28(23):3013-20
pubmed: 23024010
J Clin Invest. 2016 Jun 1;126(6):2267-79
pubmed: 27140397
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):10461-10466
pubmed: 28893982
Cell Mol Life Sci. 2019 May;76(10):2015-2030
pubmed: 30725116
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Mol Cell Biol. 2019 Nov 12;39(23):
pubmed: 31501276
Am J Pathol. 2004 Jul;165(1):175-80
pubmed: 15215173
Cancer Sci. 2003 Apr;94(4):344-9
pubmed: 12824902
Trends Endocrinol Metab. 2016 Jun;27(6):415-426
pubmed: 27113082
Oncogene. 2018 Aug;37(35):4871-4886
pubmed: 29773901
Mol Cell Biol. 2015 Apr;35(7):1223-37
pubmed: 25605330
RNA. 2002 Sep;8(9):1102-11
pubmed: 12358429
Cell Metab. 2018 Feb 6;27(2):404-418.e7
pubmed: 29358041
J Exp Clin Cancer Res. 2019 Feb 13;38(1):76
pubmed: 30760284
Mol Cell. 2018 Jun 21;70(6):1038-1053.e7
pubmed: 29932899
EMBO Rep. 2008 Mar;9(3):252-9
pubmed: 18202719
Cell. 2015 Oct 8;163(2):506-19
pubmed: 26451490
Trends Cancer. 2017 Jul;3(7):506-528
pubmed: 28718405
Biomed Pharmacother. 2017 Aug;92:919-926
pubmed: 28605876