Functional Characterization of lncRNA152 as an Angiogenesis-Inhibiting Tumor Suppressor in Triple-Negative Breast Cancers.
Animals
Humans
Mice
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Neoplasm Invasiveness
/ genetics
Neovascularization, Pathologic
/ genetics
RNA-Binding Proteins
/ genetics
Triple Negative Breast Neoplasms
/ pathology
RNA, Long Noncoding
/ genetics
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
03 11 2022
03 11 2022
Historique:
received:
11
02
2022
revised:
04
07
2022
accepted:
19
08
2022
pubmed:
24
8
2022
medline:
5
11
2022
entrez:
23
8
2022
Statut:
ppublish
Résumé
Long noncoding RNAs have been implicated in many of the hallmarks of cancer. Herein, we found that the expression of lncRNA152 (lnc152; a.k.a. DRAIC), which we annotated previously, is highly upregulated in luminal breast cancer (LBC) and downregulated in triple-negative breast cancer (TNBC). Knockdown of lnc152 promotes cell migration and invasion in LBC cell lines. In contrast, ectopic expression of lnc152 inhibits growth, migration, invasion, and angiogenesis in TNBC cell lines. In mice, lnc152 inhibited the growth of TNBC cell xenografts, as well as metastasis of TNBC cells in an intracardiac injection model. Transcriptome analysis of the xenografts indicated that lnc152 downregulates genes controlling angiogenesis. Using pull down assays followed by LC/MS-MS, we identified RBM47, a known tumor suppressor in breast cancer, as a lnc152-interacting protein. The effects of lnc152 in TNBC cells are mediated, in part, by regulating the expression of RBM47. Collectively, our results demonstrate that lnc152 is an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC. This study identifies lncRNA152 as an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC by upregulating the expression of the tumor suppressor RBM47. As such, lncRNA152 may serve as a biomarker to track aggressiveness of breast cancer, as well as therapeutic target for treating TNBC.
Identifiants
pubmed: 35997635
pii: 708417
doi: 10.1158/1541-7786.MCR-22-0123
pmc: PMC9633386
mid: NIHMS1833299
doi:
Substances chimiques
RBM47 protein, human
0
RNA-Binding Proteins
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1623-1635Subventions
Organisme : NCI NIH HHS
ID : P30 CA142543
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK058110
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK069710
Pays : United States
Organisme : NIH HHS
ID : S10 OD021684
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
Références
Cancer Gene Ther. 2022 Jul;29(7):951-960
pubmed: 34645975
Commun Biol. 2020 Feb 5;3(1):56
pubmed: 32024996
J Cancer. 2017 Sep 12;8(16):3131-3141
pubmed: 29158785
Cell Mol Biol Lett. 2020 Apr 25;25:29
pubmed: 32351584
Mol Cell. 2019 Sep 19;75(6):1270-1285.e14
pubmed: 31351877
Drug Deliv Transl Res. 2018 Oct;8(5):1483-1507
pubmed: 29978332
Front Genet. 2020 Nov 30;11:527484
pubmed: 33329688
Cancer Res. 2017 Aug 1;77(15):3965-3981
pubmed: 28701486
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Semin Cancer Biol. 2015 Dec;35:85-95
pubmed: 26319607
Nucleic Acids Res. 2013 May;41(9):4976-87
pubmed: 23558749
Elife. 2014 Jun 04;3:
pubmed: 24898756
Int J Oncol. 2016 Nov;49(5):1773-1784
pubmed: 27826619
Mol Cell. 2015 Aug 20;59(4):698-711
pubmed: 26236012
Cancer Res. 2020 Mar 1;80(5):950-963
pubmed: 31900260
Theranostics. 2018 Jun 8;8(13):3654-3675
pubmed: 30026873
Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102
pubmed: 28407145
Mol Cell. 2015 Apr 2;58(1):21-34
pubmed: 25752574
Cancer Res. 2019 Jun 15;79(12):3011-3027
pubmed: 31053634
Nat Biotechnol. 2010 May;28(5):511-5
pubmed: 20436464
Cell. 2016 Mar 24;165(1):45-60
pubmed: 27015306
Nat Protoc. 2010 Apr;5(4):628-35
pubmed: 20224563
Cancer Res. 2019 Jun 15;79(12):3050-3062
pubmed: 30796052
J Cell Sci. 2021 Dec 15;134(24):
pubmed: 34746949
Nature. 2000 Aug 17;406(6797):747-52
pubmed: 10963602
Endocr Rev. 2015 Feb;36(1):25-64
pubmed: 25426780
Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4415-21
pubmed: 17671124
Surg Oncol. 2020 Sep;34:31-39
pubmed: 32891348
Nat Genet. 2018 Dec;50(12):1705-1715
pubmed: 30349115
Genome Biol. 2003;4(5):P3
pubmed: 12734009
Front Oncol. 2019 Oct 24;9:1091
pubmed: 31709179
Oncogene. 2019 Jun;38(26):5127-5141
pubmed: 30872794
J Egypt Natl Canc Inst. 2021 Jul 02;33(1):15
pubmed: 34212275
Cold Spring Harb Protoc. 2011 Aug 01;2011(8):940-9
pubmed: 21807852
Cell Death Dis. 2019 Jun 24;10(7):499
pubmed: 31235696
Genome Res. 2018 Feb;28(2):159-170
pubmed: 29273624
Exp Mol Pathol. 2020 Oct;116:104491
pubmed: 32659236
Front Oncol. 2018 Jul 02;8:248
pubmed: 30013950
Signal Transduct Target Ther. 2020 Mar 12;5(1):28
pubmed: 32296047
Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12241-12250
pubmed: 33336743
Nature. 2009 Jun 18;459(7249):1005-9
pubmed: 19421193
Cancer J. 2015 Jul-Aug;21(4):267-73
pubmed: 26222078
Breast Cancer Res Treat. 2012 Feb;131(3):881-90
pubmed: 21503684
Genome Biol. 2013 Apr 25;14(4):R36
pubmed: 23618408
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Mol Cancer Res. 2015 May;13(5):828-38
pubmed: 25700553
Nat Rev Mol Cell Biol. 2021 Feb;22(2):96-118
pubmed: 33353982
Cancers (Basel). 2020 Oct 31;12(11):
pubmed: 33142861
Cancer Cell. 2016 Apr 11;29(4):452-463
pubmed: 27070700