ncRNA basic information
ncRNA ID:
MIMAT0000232
ncRNA Database:
miRBase
ncRNA Name:
miR-199a-3p
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
RT-PCR
ncRNA Target Gene:
mTOR
ncRNA Pathway:
mTOR signaling pathway
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00515 (APRD00359)
Drug Name:
Cisplatin
Drug Method:
In this study, we demonstrate the essential role and mechanism of miR-199a-3p in regulating cisplatin sensitivity in cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that expression of miR-199a-3p was positively correlated with cisplatin sensitivity in cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the proliferation rate and increase apoptosis of cholangiocarcinoma cells in the presence of cisplatin, while miR-199a-3p inhibition had the opposite effect. Further study demonstrated that mTOR was the target gene of miR-199a-3p, and that miR-199a-3p mimics could inhibit expression of mTOR, which consequently reduced the phosphorylation of its downstream proteins 4EBP1 and p70s6k. Rescue experiments proved that miR-199a-3p could increase the cisplatin sensitivity of cholangiocarcinoma cell lines by regulating mTOR expression. Moreover, we also found that miR-199a-3p overexpression could reduce cisplatin induced MDR1 expression by decreasing the synthesis and increasing the degradation of MDR1, thus enhancing the effectiveness of cisplatin in cholangiocarcinoma. In conclusion, miR-199a-3p could increase cisplatin sensitivity of cholangiocarcinoma cell lines by inhibiting the activity of the mTOR signaling pathway and decreasing the expression of MDR1.
Drug Response:
sensitive
Cancer basic information
Cancer:
cholangiocarcinoma
Tissue/Cell:
cell line (RBE, GBC-SD )
Other information
Title:
MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1.
Journal:
Oncotarget
Published:
2017
PubMed ID:
28422725