Retraction Note: Aberrant mannosylation profile and FTX/miR-342/ALG3-axis contribute to development of drug resistance in acute myeloid leukemia
2018
Drug-resistance is a major problem in acute myeloid leukemia (AML)
chemotherapy. Aberrant changes in specific N-glycans have been observed in leukemia multidrug resistance (MDR).
MicroRNAs (miRNAs) and long non coding RNAs (lncRNAs) act as key players in the
development of AML resistance to chemotherapy. In the present study, the N-glycan profiles of membrane proteins were analyzed
from adriamycin (ADR)-resistant U937/ADR cells and sensitive line U937 cells using
mass spectrometry (MS). The composition profiling of high-mannose N-glycans differed in U937/ADR and U937 cell lines.
Lectin microarray showed that the strong binding of membrane proteins was observed
for MAN-M and ConA lectins, which were specific for mannose. These binding were also
validated by flow cytometry. Importantly, the alteration of high-mannose N-glycan was further confirmed by detecting the enzyme
level of ALG family. The altered level of ALG3 was found corresponding to the
drug-resistant phenotype of AML cell lines both in vitro and in vivo.
Mechanistically, miR-342 was found to be dysregulated and inversely correlated to
ALG3 expression, targeting its 3′-UTR. LncRNA FTX was a direct target of miR-342 and
positively modulated ALG3 expression by competitively binding miR-342 in AML cell
lines. Functionally, we found that FTX directly interacted with miR-342 to regulate
ALG3 expression and function, including ADR-resistant cell growth and apoptosis. The
observation suggested that high-mannose N-glycans
and mannosyltransferase ALG3 affected drug-resistance in AML cells. FTX/miR-342/ALG3
axis could potentially be used for the targets to overcome therapeutic resistance in
AML.
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