ncRNA basic information
ncRNA ID:
MIMAT0000231
ncRNA Database:
miRBase
ncRNA Name:
miR-199a-5p
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
RT-qPCR
ncRNA Target Gene:
WNT2
ncRNA Pathway:
WNT2-mediated Beta-catenin signaling pathway
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00619 (APRD01028, EXPT02967, DB03261)
Drug Name:
Imatinib
Drug Method:
Higher protective autophagy was identified in IM-resistant K562 (K562R) cells. Inhibition of autophagy by the inhibitors, chloroquine and 3-methyladenine, enhanced IMs efficacy in K562R cells. In addition, microRNA (miR)-199a/b-5p were downregulated in K562R cells compared to parent cells. Overexpression of miR-199a/b-5p reduced autophagy and induced cell apoptosis, resulting in enhanced IMs efficacy in K562R cells. Moreover, expression levels of the Wingless-type MMTV integration site family member 2 (WNT2), a positive regulator of autophagy, were significantly higher in K562R cells, and it was validated as a direct target gene of miR-199a/b-5p. Overexpressions of miR-199a/b-5p inhibited WNT2 downstream signaling. Furthermore, overexpression and knockdown of WNT2 influenced autophagy formation and CML drug sensitivity to IM. Overexpression of WNT2 could also reverse miR-199a/b-5p-enhanced IM efficacy in K562R cells. These results emphasized that miR-199a/b-5p inhibited autophagy via repressing WNT2 signaling and might provide novel therapeutic strategies for future IM-resistant CML therapy and drug development.
Drug Response:
sensitive
Cancer basic information
Cancer:
chronic myeloid leukemia
Tissue/Cell:
cell line (K562, K562R, KU812, and KU812R)
Other information
Title:
microRNA-199a/b-5p enhance imatinib efficacy via repressing WNT2 signaling-mediated protective autophagy in imatinib-resistant chronic myeloid leukemia cells.
Journal:
Chem Biol Interact
Published:
2018
PubMed ID:
29890129