ncRNA basic information
ncRNA ID:
MI0003514
ncRNA Database:
miRBase
ncRNA Name:
miR-539
ncRNA Type:
miRNA
ncRNA Expression:
down-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
DCLK1
ncRNA Pathway:
P13?K/AKT/mTOR signaling pathway
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00515 (APRD00359)
Drug Name:
Cisplatin
Drug Method:
In this study, we found that miR-539 was significantly downregulated in DDP-resistant cell lines (A549/DDP and H1299/DDP). Overexpression of miR-539 enhanced the sensitivity of DDP-resistant NSCLC cells to DDP by suppressing cell proliferation, causing cell cycle arrest, inducing apoptosis, repressing invasion and migration. Whereas, downregulation of miR-539 inhibited the sensitivity of parental NSCLC cells to DDP by promoting cell proliferation and decreasing DDP-induced apoptosis. Furthermore, the luciferase report assay identified doublecortin-like kinase 1 (DCLK1) was a direct target of miR-539. Knockdown of DCLK1 mimicked the function of miR-539-mediated cell chemosensitivity in DDP-resistant NSCLC cells, while restoration of DCLK1 reversed the effect of miR-539 overexpression. We also found that P13-K/AKT/mTOR signaling pathway was also involved in miR-539/DCLK1 axis -mediated chemosensitivity in DDP-resistant NSCLC cells. Additionally, the downregulation of miR-539 was closely correlated with severe clinicopathological parameters including the upregulation of DCLK1, chemosensitivity to DDP, and tumor aggressiveness in NSCLC patients. In conclusion, miR-539 increased the chemosensitivity to DDP in NSCLC cells by directly targeting DCLK1, which might provide potential biomarkers for DDP-resistant NSCLC therapy.
Drug Response:
resistant
Cancer basic information
Cancer:
lung non-small cell carcinoma
Tissue/Cell:
cell line ( A549,A549/DDP,H1299,H1299/DDP)
Other information
Title:
miR-539 enhances chemosensitivity to cisplatin in non-small cell lung cancer by targeting DCLK1.
Journal:
Biomed Pharmacother
Published:
2018
PubMed ID:
30119173