Knockdown of long non-coding RNA HOTAIR reverses cisplatin resistance of ovarian cancer cells through inhibiting miR-138-5p-regulated EZH2 and SIRT1.
Apoptosis
/ drug effects
Cell Line, Tumor
Cisplatin
/ pharmacology
Drug Resistance, Neoplasm
/ genetics
Enhancer of Zeste Homolog 2 Protein
/ antagonists & inhibitors
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Knockout Techniques
/ methods
Humans
MicroRNAs
/ antagonists & inhibitors
Ovarian Neoplasms
/ genetics
RNA, Long Noncoding
/ genetics
Real-Time Polymerase Chain Reaction
Sirtuin 1
/ antagonists & inhibitors
Up-Regulation
DDP resistance
HOTAIR
Ovarian cancer
miR-138-5p
Journal
Biological research
ISSN: 0717-6287
Titre abrégé: Biol Res
Pays: England
ID NLM: 9308271
Informations de publication
Date de publication:
29 Apr 2020
29 Apr 2020
Historique:
received:
28
07
2019
accepted:
17
04
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
8
5
2020
Statut:
epublish
Résumé
Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells.
METHODS
METHODS
DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP.
RESULTS
RESULTS
We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor.
CONCLUSIONS
CONCLUSIONS
These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.
Identifiants
pubmed: 32349783
doi: 10.1186/s40659-020-00286-3
pii: 10.1186/s40659-020-00286-3
pmc: PMC7191713
doi:
Substances chimiques
MIRN138 microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
EZH2 protein, human
EC 2.1.1.43
Enhancer of Zeste Homolog 2 Protein
EC 2.1.1.43
SIRT1 protein, human
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
18Subventions
Organisme : Natural Science Foundation of Liaoning Province
ID : 20170540339
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