ncRNA basic information
ncRNA ID:
MI0000290
ncRNA Database:
miRBase
ncRNA Name:
miR-214
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
RT-qPCR
ncRNA Target Gene:
netrin-1
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00515 (APRD00359)
Drug Name:
Cisplatin
Drug Method:
The present study aimed to clarify the biological function of miR-214 and potential mechanisms in chemoresistance of bladder cancer cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that miR-214 was downregulated in bladder cancer tissues compared with the level in normal tissues. miR-214 was downregulated in bladder cancer cell lines compared with the level in the normal cell line SV-HUC-1. miR-214 mimics were transfected into T24 and J82 cell lines to restore its expression. The results indicated that miR-214 mimic inhibited proliferation and invasion in these cell lines. In addition, miR-214 mimic reduced cisplatin resistance in T24 and J82 cells, indicated by the inhibition of cell viability and upregulation of cell apoptosis. Western blotting demonstrated that miR-214 mimic was able to upregulate cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), while downregulate caspase-3 and PARP expression, and AKT phosphorylation. Using prediction software, it was revealed that the netrin-1 oncoprotein is on the target list of miR-214. miR-214 also downregulated netrin-1 protein and mRNA expression levels in the T24 and J82 cell lines. Luciferase reporter assays demonstrated that netrin-1 acted as a direct target of miR-214. A negative correlation between netrin-1 and miR-214 expression in bladder cancer tissues was also observed. In addition, cisplatin treatment could induce netrin-1 protein expression in bladder cancer cells and miR-214 mimic partly blocked this phenomenon. Netrin-1 plasmid transfection inhibited cisplatin-induced apoptosis, upregulated AKT phosphorylation, and downregulated caspase-3 and PARP cleavage. Netrin-1 was restored in cells transfected with miR-214 mimic using plasmid transfection. Netrin-1 transfection restored AKT phosphorylation and blocked caspase/PARP cleavage in the T24 and J82 cell lines. In conclusion, the present study demonstrated that miR-214 is downregulated in bladder cancer tissues and cell lines. miR-214 reduces chemoresistance by targeting netrin-1 in bladder cancer cell lines.
Drug Response:
sensitive
Cancer basic information
Cancer:
bladder cancer
Tissue/Cell:
cell line (SV-HUC-1, RT-4, J82 and T24 )
Other information
Title:
miR-214 reduces cisplatin resistance by targeting netrin-1 in bladder cancer cells.
Journal:
Int J Mol Med
Published:
2018
PubMed ID:
29328435