ncRNA basic information
ncRNA ID:
MI0003130
ncRNA Database:
miRBase
ncRNA Name:
miR-202
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
RT-PCR
ncRNA Target Gene:
HK2
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00619 (APRD01028, EXPT02967, DB03261)
Drug Name:
Imatinib
Drug Method:
In the present study, we aimed to investigate the roles of miR-202 in the regulation of imatinib sensitivity in CML cell lines and the possible mechanisms involved in this process. We found miR-202 was down-regulated in seven CML cell lines by quantitative reverse-transcription PCR (qRT-PCR) analysis. Overexpression of miR-202 significantly suppressed proliferation rates of CML cells. By establishing imatinib resistant cell lines originating from K562 and KU812 cells, we observed expressions of miR-202 were down-regulated by imatinib treatments and imatinib resistant CML cell lines exhibited lower level of miR-202 On the contrary, imatinib resistant CML cell lines displayed up-regulated glycolysis rate than sensitive cells with the evidence that glucose uptake, lactate production, and key glycolysis enzymes were elevated in imatinib resistant cells. Importantly, the imatinib resistant CML cell lines were more sensitive to glucose starvation and glycolysis inhibitors. In addition, we identified Hexokinase 2 (HK2) as a direct target of miR-202 in CML cell lines. Overexpression of miR-202 sensitized imatinib resistant CML through the miR-202-mediated glycolysis inhibition by targetting HK2. Finally, we provided the clinical relevance that miR-202 was down-regulated in CML patients and patients with lower miR-202 expression displayed higher HK2 expression. The present study will provide new aspects on the miRNA-modulated tyrosine kinase inhibitor (TKI) sensitivity in CML, contributing to the development of new therapeutic anticancer drugs.
Drug Response:
sensitive
Cancer basic information
Cancer:
chronic myeloid leukemia
Tissue/Cell:
cell line (K562, KU812,EM2, EM3, LAMA 84, KCL-22, and HL-60 )
Other information
Title:
Overexpression of miR-202 resensitizes imatinib resistant chronic myeloid leukemia cells through targetting Hexokinase 2.
Journal:
Biosci Rep
Published:
2018
PubMed ID:
29559564