ncRNA basic information
ncRNA ID:
MI0000293
ncRNA Database:
miRBase
ncRNA Name:
miR-217
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
qPCR
ncRNA Target Gene:
AGR2
ncRNA Pathway:
miR-217/AGR2 pathway
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB01254
Drug Name:
Dasatinib
Drug Method:
In this study, we observed an increased level of AGR2 in TKI-resistant CML cells. Silence of AGR2 in dasatinib-resistant K562 (K562DR) cells led to restored sensitivity to dasatinib both in vitro and in vivo. Exposure to dasatinib induced upregulation of AGR2 in K562 cells, which indicated a probable treatment-related drug resistance. We further investigated the potential interaction between microRNA (miRNA) and AGR2 in K562DR cells and found that downregulation of miR-217 was associated with overexpression of AGR2 in K562DR cells. Luciferase reporter assay identified that miR-217 negatively regulated expression of AGR2 through binding the 3-untranslated region of AGR2. Hypermethylation of the CpG island on the promoter region of the MIR217 gene is a probable reason for the downregulation of miR-217 in dasatinib-treated K562 cells. Forced expression of miR-217 led to decreased expression of AGR2 as well as compromised TKI-resistant potential of K562DR cells. Similarly, overexpression of miR-217 resensitized K562DR cells to dasatinib treatment in a murine xenograft transplantation model. TKI treatment-induced drug resistance is correlated with a decrease of miR-217 and upregulation of AGR2. The miR-217/AGR2 interaction might be a potential therapeutic target in treating CML patients with TKI resistance.
Drug Response:
sensitive
Cancer basic information
Cancer:
chronic myeloid leukemia
Tissue/Cell:
tissue and cell line (K562, KCL22 and KU812)
Other information
Title:
miR-217 sensitizes chronic myelogenous leukemia cells to tyrosine kinase inhibitors by targeting pro-oncogenic anterior gradient 2.
Journal:
Exp Hematol
Published:
2018
PubMed ID:
30195077