Exosomal microRNA‑146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2‑mediated PI3K/Akt axis.
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:
Aug 2020
Aug 2020
Historique:
received:
12
02
2020
accepted:
04
05
2020
entrez:
7
7
2020
pubmed:
7
7
2020
medline:
9
3
2021
Statut:
ppublish
Résumé
The carrier role of exosomes from human umbilical cord mesenchymal stem cells (hUCMSCs) containing microRNAs (miRNAs) has been implicated in gene and drug therapy. The aim of the present study was to investigate the role of exosomal microRNA‑146a (miR‑146a) from hUCMSCs in ovarian cancer (OC). Following the generation of docetaxel (DTX)‑resistant SKOV3 cells and taxane‑resistant A2780 cells, exosomes were isolated from hUCMSCs and added to the chemoresistant cells. Microarray analysis revealed that miR‑146a expression was upregulated in DTX/SKOV3 cells among 15 ectopically expressed miRNAs. Analysis using the StarBase and miRSearch databases demonstrated that miR‑146a targeted laminin γ2 (LAMC2), which was further verified using dual‑luciferase reporter assays. Subsequently, miR‑146a inhibitor or LAMC2 overexpression vectors were transfected into hUCMSCs or OC cells, respectively, and their effects on growth and chemoresistance in OC cells were assessed. The hUCMSC‑derived exosomes reduced cell growth and chemoresistance in OC. Furthermore, hUCMSC‑derived exosomes with miR‑146a expression knocked down increased OC cell growth and chemoresistance, which was mediated by the PI3K/Akt signaling pathway via LAMC2.
Identifiants
pubmed: 32626953
doi: 10.3892/ijmm.2020.4634
pmc: PMC7307828
doi:
Substances chimiques
LAMC2 protein, human
0
Laminin
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
609-620Références
Lancet Oncol. 2019 Jun;20(6):754-755
pubmed: 31076364
Life Sci. 2020 Aug 1;254:116801
pubmed: 31472145
Mol Pharm. 2011 Feb 7;8(1):260-9
pubmed: 21166459
Sci Rep. 2019 Nov 14;9(1):16743
pubmed: 31727903
Cancer Lett. 2019 Feb 1;442:351-361
pubmed: 30419348
Ann Med. 2015;47(5):359-69
pubmed: 26158617
Cytotherapy. 2006;8(4):315-7
pubmed: 16923606
Anticancer Res. 2019 Aug;39(8):4023-4030
pubmed: 31366484
Sci Rep. 2016 Dec 06;6:38339
pubmed: 27922090
Mol Hum Reprod. 2019 Nov 30;25(11):755-771
pubmed: 31588496
Cancer Cell Int. 2019 Dec 21;19:347
pubmed: 31889899
Cell Transplant. 2012;21(7):1515-27
pubmed: 22732188
J Hepatol. 2016 Mar;64(3):609-17
pubmed: 26592953
J Clin Invest. 2013 May;123(5):2143-54
pubmed: 23619365
Exp Cell Res. 2020 Mar 1;388(1):111823
pubmed: 31926946
Cell Cycle. 2020 Jan;19(2):193-206
pubmed: 31885310
Int J Clin Exp Pathol. 2019 Jul 01;12(7):2474-2484
pubmed: 31934074
Oncogene. 2020 Feb;39(7):1600-1616
pubmed: 31700155
Cell Oncol (Dordr). 2018 Aug;41(4):463
pubmed: 30047093
Biotechnol Adv. 2013 Sep-Oct;31(5):543-51
pubmed: 22959595
Life Sci. 2019 Sep 1;232:116648
pubmed: 31301414
Mol Cell Proteomics. 2013 Oct;12(10):2820-32
pubmed: 23798558
Br J Cancer. 2012 Jun 5;106(12):1901-6
pubmed: 22596239
Front Oncol. 2019 Oct 22;9:1076
pubmed: 31696054
Cancer Sci. 2015 Dec;106(12):1730-7
pubmed: 26450632
J Control Release. 2016 Aug 10;235:147-154
pubmed: 27238440
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
Mol Cancer. 2017 Feb 1;16(1):31
pubmed: 28148268
Genomics Proteomics Bioinformatics. 2015 Feb;13(1):17-24
pubmed: 25724326
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Br J Cancer. 2015 Jul 28;113(3):484-91
pubmed: 26180921
Int J Cancer. 2019 Oct 15;145(8):2209-2224
pubmed: 30980673
Cancers (Basel). 2019 Nov 13;11(11):
pubmed: 31766284
Pharmacol Ther. 2019 Aug;200:42-54
pubmed: 30998940
Oncol Res. 2016;23(6):275-82
pubmed: 27131313
Cell Death Differ. 2018 Nov;25(11):1980-1995
pubmed: 29511340