Long noncoding RNA HOST2, working as a competitive endogenous RNA, promotes STAT3-mediated cell proliferation and migration via decoying of let-7b in triple-negative breast cancer.
HOST2
Let-7b
STAT3
TNBC
ceRNA
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
05 Apr 2020
05 Apr 2020
Historique:
received:
18
01
2020
accepted:
12
03
2020
entrez:
7
4
2020
pubmed:
7
4
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Human ovarian cancer specific transcript 2 (HOST2) is a long non-coding RNA (lncRNA) reported to be specifically high expressed in human ovarian cancer. However, the mechanism that how HOST2 regulates triple negative breast cancer (TNBC) need to be explored. In this study, expression of HOST2 was determined in 40 TNBC patients and matched non-cancerous tissues by qRT-PCR and in situ hybridization (ISH) assay. The biological functions of HOST2 was measured by losing features. The effect of HOST2 on viability, proliferation and migration was evaluated by MTT, colony formation assay, EDU analysis, transwell invasion assay and nude mouse xenograft model. Fluorescence in situ hybridization (FISH), Luciferase report assay, RNA immunoprecipitation (RIP) assay and Western blot were fulfilled to measure molecular mechanisms. The results showed that HOST2 was up-regulated in BC tissues and cell lines. Clinical outcome analysis demonstrated that high expression of HOST2 was associated with poor prognosis of TNBC patients. Functional experiments illustrated that knockdown of HOST2 significantly suppressed TNBC cell proliferation and migration. Western blot assays, qRT-PCR assays, RIP assays and luciferase reporter assays revealed that HOST2 regulated STAT3 via crosstalk with let-7b. Depression of HOST2 suppressed STAT3-mediated proliferation and migration in TNBC cells. HOST2 could function as a decoy of let-7b to depress expression of STAT3. HOST2 could function as a oncogene and promoted STAT3-mediated proliferation and migration through acting as a competing endogenous RNA, which might act as a potential biomarker for TNBC patients.
Sections du résumé
BACKGROUND
BACKGROUND
Human ovarian cancer specific transcript 2 (HOST2) is a long non-coding RNA (lncRNA) reported to be specifically high expressed in human ovarian cancer. However, the mechanism that how HOST2 regulates triple negative breast cancer (TNBC) need to be explored.
METHODS
METHODS
In this study, expression of HOST2 was determined in 40 TNBC patients and matched non-cancerous tissues by qRT-PCR and in situ hybridization (ISH) assay. The biological functions of HOST2 was measured by losing features. The effect of HOST2 on viability, proliferation and migration was evaluated by MTT, colony formation assay, EDU analysis, transwell invasion assay and nude mouse xenograft model. Fluorescence in situ hybridization (FISH), Luciferase report assay, RNA immunoprecipitation (RIP) assay and Western blot were fulfilled to measure molecular mechanisms.
RESULTS
RESULTS
The results showed that HOST2 was up-regulated in BC tissues and cell lines. Clinical outcome analysis demonstrated that high expression of HOST2 was associated with poor prognosis of TNBC patients. Functional experiments illustrated that knockdown of HOST2 significantly suppressed TNBC cell proliferation and migration. Western blot assays, qRT-PCR assays, RIP assays and luciferase reporter assays revealed that HOST2 regulated STAT3 via crosstalk with let-7b. Depression of HOST2 suppressed STAT3-mediated proliferation and migration in TNBC cells. HOST2 could function as a decoy of let-7b to depress expression of STAT3.
CONCLUSIONS
CONCLUSIONS
HOST2 could function as a oncogene and promoted STAT3-mediated proliferation and migration through acting as a competing endogenous RNA, which might act as a potential biomarker for TNBC patients.
Identifiants
pubmed: 32248842
doi: 10.1186/s13046-020-01561-7
pii: 10.1186/s13046-020-01561-7
pmc: PMC7132993
doi:
Substances chimiques
LncRNA-HOST2, human
0
MicroRNAs
0
RNA, Long Noncoding
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
mirnlet7 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
58Subventions
Organisme : National Natural Science Foundation of China
ID : 82172240
Références
Asian Pac J Cancer Prev. 2016;17(4):1595-608
pubmed: 27221827
J Cell Biochem. 2018 Jun;119(6):4570-4580
pubmed: 29236319
J Clin Diagn Res. 2017 Jan;11(1):EC05-EC08
pubmed: 28273970
IUBMB Life. 2019 Jan;71(1):93-104
pubmed: 30290058
J Exp Clin Cancer Res. 2019 Nov 6;38(1):455
pubmed: 31694696
Cell Physiol Biochem. 2018;51(1):301-314
pubmed: 30453302
Cancer Cell Int. 2019 Nov 1;19:275
pubmed: 31695578
Oncotarget. 2018 Apr 3;9(25):17825-17838
pubmed: 29707149
Neoplasma. 2019 Jan 15;66(1):101-108
pubmed: 30509094
Thorac Cancer. 2017 Nov;8(6):582-591
pubmed: 28834648
Front Oncol. 2019 Aug 27;9:834
pubmed: 31508377
Biosci Rep. 2017 Apr 20;37(2):
pubmed: 28143959
Nat Rev Mol Cell Biol. 2008 Jan;9(1):22-32
pubmed: 18073770
Nat Rev Cancer. 2014 Nov;14(11):736-46
pubmed: 25342631
Mol Oncol. 2020 Jan;14(1):180-196
pubmed: 31637848
Biophys Rev. 2019 Apr;11(2):227-234
pubmed: 30796734
Noncoding RNA Res. 2019 Feb 05;4(1):36-44
pubmed: 30891536
Front Oncol. 2019 May 31;9:407
pubmed: 31214490
Am J Cancer Res. 2018 Jan 01;8(1):192-206
pubmed: 29416932
Breast Cancer. 2019 Nov;26(6):784-791
pubmed: 31197620
Oncol Lett. 2015 Apr;9(4):1907-1911
pubmed: 25789066
Cell. 2011 Oct 14;147(2):358-69
pubmed: 22000014
Cell Oncol (Dordr). 2019 Feb;42(1):1-12
pubmed: 30361825
Cell Physiol Biochem. 2018;48(1):16-28
pubmed: 30001527
J Exp Clin Cancer Res. 2019 Oct 28;38(1):430
pubmed: 31661003
Cell Death Dis. 2019 Aug 5;10(8):585
pubmed: 31383847
Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):8751-8760
pubmed: 31696461
Biomed Pharmacother. 2019 Feb;110:294-301
pubmed: 30522015
Cancer Immunol Immunother. 2018 Jan;67(1):13-23
pubmed: 28875329
Onco Targets Ther. 2019 Aug 28;12:6991-7004
pubmed: 31695414
Clin Cancer Res. 2012 Sep 15;18(18):5144-53
pubmed: 22847808
Cancer Cell Int. 2018 Nov 12;18:179
pubmed: 30459529
J Cell Physiol. 2019 Jul;234(7):10080-10100
pubmed: 30537129
Wiley Interdiscip Rev RNA. 2018 May;9(3):e1471
pubmed: 29516680
Eur Rev Med Pharmacol Sci. 2019 Mar;23(6):2380-2390
pubmed: 30964163
Expert Rev Mol Diagn. 2018 Nov;18(11):963-979
pubmed: 30338716
Cell. 2005 Nov 18;123(4):631-40
pubmed: 16271387
Ann Oncol. 2017 Feb 1;28(2):208-217
pubmed: 27831505
Hum Mol Genet. 2015 Feb 1;24(3):841-52
pubmed: 25292198
Theranostics. 2019 Oct 1;9(24):7384-7402
pubmed: 31695775
Nat Rev Genet. 2004 Jul;5(7):522-31
pubmed: 15211354
Cell. 2011 Aug 5;146(3):353-8
pubmed: 21802130
BMB Rep. 2018 Jun;51(6):280-289
pubmed: 29636120
Oncogene. 2003 Oct 16;22(46):7225-32
pubmed: 14562052
J Exp Clin Cancer Res. 2019 May 14;38(1):195
pubmed: 31088482
Int J Cancer. 2016 Jun 1;138(11):2570-8
pubmed: 26559373