Downregulation of miR-145-5p in cancer cells and their derived exosomes may contribute to the development of ovarian cancer by targeting CT.
Carcinogenesis
/ genetics
Cell Line, Tumor
Connective Tissue Growth Factor
/ genetics
Down-Regulation
/ genetics
Exosomes
/ metabolism
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Kaplan-Meier Estimate
MicroRNAs
/ metabolism
Middle Aged
Ovarian Neoplasms
/ genetics
Prognosis
Journal
International journal of molecular medicine
ISSN: 1791-244X
Titre abrégé: Int J Mol Med
Pays: Greece
ID NLM: 9810955
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
10
05
2018
accepted:
11
09
2018
pubmed:
27
10
2018
medline:
6
3
2019
entrez:
27
10
2018
Statut:
ppublish
Résumé
The present study aimed to identify shared microRNAs (miRNAs) in ovarian cancer (OC) cells and their exosomes using microarray data (accession number GSE103708) available from the Gene Expression Omnibus database, including exosomal samples from 13 OC cell lines and 3 normal ovarian surface epithelial cell lines, and their original cell samples. Differentially expressed miRNAs (DE‑miRNAs) were identified using the Linear Models for Microarray data method, and mRNA targets of DE‑miRNAs were predicted using the miRWalk2 database. The potential functions of target genes were analyzed using Database for Annotation, Visualization and Integrated Discovery and intersected with known OC‑associated pathways downloaded from the Comparative Toxicogenomics Database. The associations between crucial miRNAs and target genes, and their clinical associations, were validated using data from The Cancer Genome Atlas. As a result, 16 upregulated and 6 downregulated DE‑miRNAs were shared in OC cell lines and their exosomes compared with normal controls. The target genes of 11 common DE‑miRNAs were predicted. Among these DE‑miRNAs, a low expression of homo sapiens (hsa)‑miR‑145‑5p was significantly correlated with a poor prognosis and higher stages. Although 91 target genes were predicted for hsa‑miR‑145‑5p, only 4 genes [connective tissue growth factor (CTGF), myotubularin‑related protein 14, protein phosphatase 3 catalytic subunit alpha and suppressor of cytokine signaling 7] were suggested as risk factors for prognosis. The subsequent Pearson's correlation analysis validated a significant negative correlation between hsa‑miR‑145‑5p and CTGF (r=‑0.1126, P=0.02188). According to the results of the functional analysis, CTGF is involved in the Hippo signaling pathway (hsa04390). In conclusion, decreased expression of hsa‑miR‑145 in OC and OC‑derived exosomes may be a crucial biomarker for the diagnosis and treatment of OC.
Identifiants
pubmed: 30365097
doi: 10.3892/ijmm.2018.3958
pmc: PMC6257844
doi:
Substances chimiques
CCN2 protein, human
0
MIRN145 microRNA, human
0
MicroRNAs
0
Connective Tissue Growth Factor
139568-91-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
256-266Références
Med Sci Monit. 2016 Oct 23;22:3925-3934
pubmed: 27771733
Breast Cancer Res. 2016 Sep 08;18(1):90
pubmed: 27608715
Cancer Metastasis Rev. 2010 Dec;29(4):613-39
pubmed: 20922462
Onco Targets Ther. 2017 May 23;10:2701-2709
pubmed: 28579808
Eur Rev Med Pharmacol Sci. 2016 Jul;20(14):3026-30
pubmed: 27460730
Nature. 2009 Jul 23;460(7254):529-33
pubmed: 19626115
Oncol Lett. 2017 Dec;14(6):6923-6928
pubmed: 29344125
Oncotarget. 2016 Mar 29;7(13):16923-35
pubmed: 26943577
Oncotarget. 2015 Apr 20;6(11):8676-86
pubmed: 25895125
Cell Rep. 2014 Sep 11;8(5):1432-46
pubmed: 25159140
Oncogenesis. 2016 Aug 08;5(8):e250
pubmed: 27500388
Oncotarget. 2016 May 10;7(19):28460-87
pubmed: 27072587
J Cell Biochem. 2018 Jun;119(6):4711-4716
pubmed: 29278659
Nat Rev Genet. 2014 Sep;15(9):599-612
pubmed: 25022902
Int J Mol Sci. 2013 Sep 23;14(9):19257-75
pubmed: 24065105
Oncotarget. 2016 May 10;7(19):28160-8
pubmed: 27058413
Oncotarget. 2016 Jul 12;7(28):43076-43087
pubmed: 27172798
Gynecol Oncol. 2015 Dec;139(3):513-9
pubmed: 26472353
Oncotarget. 2017 Jun 27;8(26):42125-42135
pubmed: 28178672
Nucleic Acids Res. 2017 Jan 4;45(D1):D972-D978
pubmed: 27651457
Cancer. 1998 Mar 1;82(5):893-901
pubmed: 9486579
Cancer Biol Ther. 2013 May;14(5):390-8
pubmed: 23380592
Semin Surg Oncol. 1994 Jan-Feb;10(1):31-46
pubmed: 8115784
CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32
pubmed: 26808342
Cancer Invest. 2015 Jul;33(6):251-8
pubmed: 25951106
Cancer Res. 2016 Dec 15;76(24):7194-7207
pubmed: 27742688
Nat Commun. 2018 Jan 15;9(1):191
pubmed: 29335551
Oncotarget. 2014 Nov 15;5(21):10816-29
pubmed: 25333261
Exp Ther Med. 2018 Feb;15(2):1672-1679
pubmed: 29434752
Gynecol Oncol. 2015 Jan;136(1):11-7
pubmed: 25449311
Gynecol Oncol. 2008 Jul;110(1):13-21
pubmed: 18589210
Methods Mol Biol. 2011;696:291-303
pubmed: 21063955
Cancer Res. 2016 Apr 1;76(7):1770-80
pubmed: 26992424
Cancer Lett. 2017 Jul 1;397:33-42
pubmed: 28288874
PLoS One. 2013;8(2):e54652
pubmed: 23390502
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Cell Death Differ. 2010 Feb;17(2):246-54
pubmed: 19730444
Adv Drug Deliv Rev. 2013 Mar;65(3):383-90
pubmed: 22921594
Cell Death Dis. 2018 Jan 24;9(2):92
pubmed: 29367737
Nat Methods. 2015 Aug;12(8):697
pubmed: 26226356
Oncotarget. 2016 May 24;7(21):31484-500
pubmed: 27129171
Nucleic Acids Res. 1999 Jan 1;27(1):29-34
pubmed: 9847135
Biochem Biophys Res Commun. 2013 Nov 29;441(4):693-700
pubmed: 24157791
Front Med (Lausanne). 2015 Jul 22;2:47
pubmed: 26258125
Oncotarget. 2017 Dec 20;9(5):5764-5777
pubmed: 29464032
Oncotarget. 2015 Dec 29;6(42):44551-62
pubmed: 26575166