LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972.
TP53
ceRNA
lncRNA LINC00588
miRNA-1972
osteosarcoma
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
10
2019
accepted:
24
02
2020
entrez:
9
4
2020
pubmed:
9
4
2020
medline:
9
4
2020
Statut:
epublish
Résumé
Long non-coding RNAs (lncRNAs) are being found to play an increasingly important role in the development of tumors. However, their biological functions and the underlying mechanisms remain unclear. Using information from GEO Datasets, we found that the lncRNA LINC00588 was downregulated in osteosarcoma (OS) in bone but was upregulated in the metastatic tumor present in the lung. We assessed the function of LINC00588 using both overexpression and knock-out studies. We performed colony formation assay, CCK-8 assay, flow cytometry, wound healing assay, transwell assay, and RT-qPCR assay and used a xenograft model to investigate the influence of LINC00588 on cell proliferation, viability, cell apoptosis and cycle, migration, invasion, endothelial cell function, EMT (epithelial to mesenchymal transition), and tumor growth, respectively. Overexpression of LINC00588 appeared to inhibit cell proliferation, viability, migration, invasion, endothelial cell function, EMT, and tumor growth but not apoptosis, while we got the opposite result when we knocked down LINC00588. Next, we predicted that LINC00588 bound to miRNA-1972 and significantly downregulated its expression, which we then verified through a luciferase reporter assay. Subsequently, we knocked down miR1972 and performed CCK-8 and transwell assays to demonstrate that downregulation of miRNA-1972 could substantially inhibit the viability and invasion of osteosarcoma cells. The expression of TP53 was downregulated at the protein level but not at the mRNA level after the overexpression of miRNA-1972. Taken together, our findings indicate that LINC00588 plays a role in OS development by downregulating the expression of miRNA-1972, which can, in turn, inhibit the expression of TP53. Hence, we believe that the LINC00588/miRNA-1072/TP53 axis could potentially serve as a therapeutic target or diagnostic biomarker for osteosarcoma.
Identifiants
pubmed: 32265694
doi: 10.3389/fphar.2020.00255
pmc: PMC7107012
doi:
Types de publication
Journal Article
Langues
eng
Pagination
255Informations de copyright
Copyright © 2020 Zhou, Zhang, Liu, Song and Shao.
Références
Int J Mol Med. 2019 Mar;43(3):1157-1166
pubmed: 30592267
Stem Cell Reports. 2018 Aug 14;11(2):395-409
pubmed: 30017820
J Clin Invest. 2009 Jun;119(6):1420-8
pubmed: 19487818
Cell Rep. 2014 Apr 10;7(1):104-12
pubmed: 24703847
Nat Rev Mol Cell Biol. 2019 Apr;20(4):199-210
pubmed: 30824861
RNA Biol. 2012 Jun;9(6):703-19
pubmed: 22664915
Nature. 2014 Jan 23;505(7484):495-501
pubmed: 24390350
Int J Clin Exp Pathol. 2015 Aug 01;8(8):8754-73
pubmed: 26464619
N Engl J Med. 1999 Jul 29;341(5):342-52
pubmed: 10423470
Nucleic Acids Res. 2012 Jan;40(Database issue):D210-5
pubmed: 22135294
Eur Rev Med Pharmacol Sci. 2019 May;23(9):3602-3610
pubmed: 31114984
Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):6813-6823
pubmed: 31486480
Cell. 2009 Nov 25;139(5):871-90
pubmed: 19945376
Nat Rev Endocrinol. 2017 Aug;13(8):480-491
pubmed: 28338660
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):260-266
pubmed: 30442366
Ann Oncol. 2010 Oct;21 Suppl 7:vii320-5
pubmed: 20943636
J Cell Biochem. 2019 Dec;120(12):19858-19867
pubmed: 31310378
Mayo Clin Proc. 2012 May;87(5):475-87
pubmed: 22560526
Oncotarget. 2015 Apr 10;6(10):7727-40
pubmed: 25762628
Cell Prolif. 2018 Dec;51(6):e12515
pubmed: 30152090
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7716-9
pubmed: 2823272
Biosci Rep. 2018 Nov 15;38(6):
pubmed: 30352834
J Cell Physiol. 2019 Aug;234(8):13464-13480
pubmed: 30624782
Oncol Lett. 2019 Jun;17(6):5403-5408
pubmed: 31186758
Biochem Biophys Res Commun. 2013 Apr 5;433(2):200-6
pubmed: 23466354
Cancer Manag Res. 2019 May 16;11:4505-4518
pubmed: 31191012
Cancer Discov. 2019 Jan;9(1):46-63
pubmed: 30266815
Eur Rev Med Pharmacol Sci. 2018 Apr;22(8):2310-2314
pubmed: 29762833
Biomed Pharmacother. 2018 Jun;102:169-174
pubmed: 29554595
Genetics. 2013 Mar;193(3):651-69
pubmed: 23463798
J Bone Oncol. 2018 Sep 22;13:76-90
pubmed: 30591861
Tumour Biol. 2016 Mar;37(3):2811-6
pubmed: 26718212
Cell Prolif. 2018 Dec;51(6):e12504
pubmed: 30182452