Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib leading to inhibition of EMT in human lung cancer.
Animals
Apoptosis
Berberine
/ pharmacology
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Survival
/ drug effects
Epithelial-Mesenchymal Transition
/ genetics
Female
Flow Cytometry
Gefitinib
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Lung Neoplasms
/ genetics
Mice
MicroRNAs
/ genetics
RNA, Long Noncoding
/ genetics
E-cadherin
EMT
HOTAIR
NSCLC
Snail
miR-34a-5p
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
12
07
2019
revised:
14
02
2020
accepted:
04
03
2020
pubmed:
6
4
2020
medline:
8
9
2021
entrez:
6
4
2020
Statut:
ppublish
Résumé
HOTAIR is an important carcinogenic lncRNA and involves in tumorigenesis, and invasion. MiR-34a-5p functions as a tumour suppressor. However, the underlying mechanism of HOTAIR regulation especially in association with miR-34a-5p in non-small-cell lung cancer (NSCLC) has not been explored. Herein, we performed series of in vitro experiments, including viability, migration, invasion, apoptosis and in vivo xenograft model, and identified that HOTAIR was remarkably elevated in NSCLC cells. Enforced HOTAIR expression promoted migration and invasion, while depleted HOTAIR diminished the ability of migration and invasion of NSCLC cells. We also observed that miR-34a-5p was dramatically inhibited in NSCLC cells and the binding correlation between HOTAIR and miR-34a-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. We also showed that induction of miR-34a-5p and reduction of HOTAIR, and the interaction between miR-34a-5p and HOTAIR resulted in the suppression of epithelial-mesenchymal transition (EMT) as illustrated by induction of key epithelial markers E-cadherin expression, reduction of vimentin and EMT-inducing transcription factor snail. Excessive expression of snail resisted miR-34a-5p-inhibited cell growth. Snail binds to E-cadherin promoter and regulates E-cadherin expression. There was a synergy in combination of berberine and gefinitib in this process. Similar findings were also observed in a tumour xenograft model. Collectively, this is the first report demonstrating reciprocal interaction of miR-34a-5p- and HOTAIR-mediated regulation of snail resulting in inhibition of EMT process by the combination of berberine and gefitinib suggesting that regulation of miR-34a-5p- and HOTAIR-mediated inhibition of EMT may provide novel treatment paradigms for lung cancer.
Identifiants
pubmed: 32248643
doi: 10.1111/jcmm.15214
pmc: PMC7214156
doi:
Substances chimiques
HOTAIR long untranslated RNA, human
0
MIRN34 microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
Berberine
0I8Y3P32UF
Gefitinib
S65743JHBS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5578-5592Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Technol Cancer Res Treat. 2017 Jan 1;:1533034617723754
pubmed: 28784052
Biomed Pharmacother. 2017 Jun;90:888-896
pubmed: 28441714
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
J Nanobiotechnology. 2018 Oct 5;16(1):76
pubmed: 30290822
Eur Rev Med Pharmacol Sci. 2017 Jan;21(1):115-119
pubmed: 28121347
CA Cancer J Clin. 2018 Jan;68(1):31-54
pubmed: 29160902
Biosci Rep. 2017 Jul 12;37(4):
pubmed: 28615347
Biochimie. 2019 May;160:193-199
pubmed: 30905732
Exp Mol Pathol. 2014 Oct;97(2):298-304
pubmed: 25102298
Oncol Lett. 2018 May;15(5):7409-7414
pubmed: 29725453
Tumour Biol. 2014 Oct;35(10):9531-8
pubmed: 25168368
Onco Targets Ther. 2016 Sep 16;9:5713-5720
pubmed: 27695348
Int J Mol Sci. 2019 Feb 16;20(4):
pubmed: 30781524
Oncogene. 2017 Dec 14;36(50):6906-6918
pubmed: 28846104
Exp Cell Res. 2018 Jul 15;368(2):137-146
pubmed: 29674112
Biomed Pharmacother. 2018 Nov;107:1447-1453
pubmed: 30257361
Exp Ther Med. 2018 Jun;15(6):4885-4889
pubmed: 29805510
Annu Rev Pathol. 2018 Jan 24;13:395-412
pubmed: 29414248
Oncol Lett. 2019 May;17(5):4726-4734
pubmed: 30944658
Sci Rep. 2018 Apr 3;8(1):5521
pubmed: 29615720
J Mol Med (Berl). 2016 Dec;94(12):1397-1409
pubmed: 27534967
J Cell Mol Med. 2018 Jan;22(1):600-612
pubmed: 28840963
J Hematol Oncol. 2014 Dec 10;7:90
pubmed: 25491133
J Cell Physiol. 2019 Apr;234(4):3478-3489
pubmed: 30367473
Cancer Manag Res. 2018 Nov 19;10:5785-5798
pubmed: 30510448
J Oncol. 2019 Jun 2;2019:5810465
pubmed: 31275381
Front Oncol. 2018 Apr 10;8:94
pubmed: 29755953
Mol Cancer Ther. 2018 May;17(5):1061-1069
pubmed: 29440295
Cell Physiol Biochem. 2018;47(3):893-913
pubmed: 29843138
Oncotarget. 2014 Sep 30;5(18):8027-38
pubmed: 25275300
Cancer Res. 2012 Nov 1;72(21):5576-87
pubmed: 22964582
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
pubmed: 24556840
Scand J Clin Lab Invest Suppl. 2016;245:S34-9
pubmed: 27435502
Biochem Biophys Res Commun. 2013 Jun 28;436(2):319-24
pubmed: 23743197
J Cell Biochem. 2020 Feb;121(2):1514-1523
pubmed: 31535411
Biochem Biophys Res Commun. 2018 Jun 27;501(3):765-770
pubmed: 29758197
Phytother Res. 2019 Mar;33(3):745-755
pubmed: 30565332
Prog Mol Biol Transl Sci. 2013;116:317-36
pubmed: 23481201
Oncotarget. 2017 May 16;8(20):32492-32504
pubmed: 28415643
Cell Death Dis. 2018 May 22;9(6):587
pubmed: 29789542
Int J Oncol. 2019 Jan;54(1):77-86
pubmed: 30431069
Exp Ther Med. 2017 Nov;14(5):4503-4508
pubmed: 29067125
Cancer Lett. 2019 Jul 10;454:90-97
pubmed: 30981759
Mol Cancer. 2014 Jun 23;13:156
pubmed: 24953832
Cancer Res. 2010 Jan 15;70(2):440-6
pubmed: 20068163
J Cell Biol. 2011 Oct 31;195(3):417-33
pubmed: 22024162
Crit Rev Oncol Hematol. 2018 Dec;132:1-8
pubmed: 30447913
Oncogene. 2017 Feb 16;36(7):942-955
pubmed: 27452518
J Cell Mol Med. 2020 May;24(10):5578-5592
pubmed: 32248643
Eur J Pharmacol. 2018 Sep 5;834:45-53
pubmed: 30017802
Cell Physiol Biochem. 2018;47(1):245-256
pubmed: 29768262
J Exp Clin Cancer Res. 2019 Feb 4;38(1):53
pubmed: 30717802
Mol Cancer. 2016 Feb 24;15:18
pubmed: 26905733
Cancer Lett. 2018 Sep 1;431:96-104
pubmed: 29859299
Med Oncol. 2017 Jul;34(7):122
pubmed: 28560682
Front Pharmacol. 2018 Nov 30;9:1413
pubmed: 30555330