ncRNA basic information
ncRNA ID:
MIMAT0002816
ncRNA Database:
miRBase
ncRNA Name:
miR-494-3p
ncRNA Type:
miRNA
ncRNA Expression:
down-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
c-MYC
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB08901 (DB06300)
Drug Name:
Ponatinib
Drug Method:
In this work, we investigated the microRNA (miRNA) expression profile of different subpopulations of CML Leukemic Stem Cells (LSCs): Lin-CD34+CD38- and Lin-CD34-CD38- cells. These cell fractions have been previously shown to be endowed with TKI intrinsic resistance. Our analysis identified 33 common deregulated miRNAs in CML LSCs. Among those, 8 miRNAs were deregulated in CML independently from BCR-ABL kinase activity and therefore are likely to be involved in the BCR-ABL-independent resistance to TKI that characterizes CML LSCs. In particular, the up-regulation of miR-29a-3p and miR-660-5p observed in CML LSCs, led to the down-regulation of their respective targets TET2 and EPAS1 and conferred TKI-resistance to CML LSCs in vitro. On the other hand, miR-494-3p down-regulation in CML LSCs, leading to c-MYC up-regulation, was able to decrease TKI-induced apoptosis. These results demonstrate that aberrant miRNA expression in CML LSCs could contribute to the intrinsic TKI-resistance observed in these cell populations, and support the development of novel therapies aimed at targeting aberrantly regulated miRNAs or their targets in order to effectively eradicate CML LSCs.
Drug Response:
resistant
Cancer basic information
Cancer:
chronic myeloid leukemia
Tissue/Cell:
cell line
Other information
Title:
Deregulated expression of miR-29a-3p, miR-494-3p and miR-660-5p affects sensitivity to tyrosine kinase inhibitors in CML leukemic stem cells.
Journal:
Oncotarget
Published:
2017
PubMed ID:
28533480