ncRNA basic information
ncRNA ID:
MIMAT0000261
ncRNA Database:
miRBase
ncRNA Name:
miR-183-5p
ncRNA Type:
miRNA
ncRNA Expression:
down-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
XIAP
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00997 (APRD00185, DB05331, DB05847)
Drug Name:
Doxorubicin
Drug Method:
In this study, we established a doxorubicin (ADM)-resistant THP-1 AML cell line (THP-1/ADM). A high-throughput microarray was used to identify circRNA expression profiles of THP-1/ADM cells and naive THP-1 cells. The identified potential functional circRNA molecule was further validated in THP-1/ADM cells and bone marrow (BM) specimens from 42 AML patients. The interactions with target microRNAs (miRNAs) and downstream messenger RNAs (mRNAs) were also explored. As a result, 49 circRNAs that are significantly differentially expressed between THP-1/ADM and THP-1 cells were identified. Of these circRNAs, downregulation of circPAN3 by small interfering RNA significantly restored ADM sensitivity of THP-1/ADM cells. Furthermore, BM samples from patients with refractory and recurrent AML showed increased expression of circPAN3. A detailed circRNA/miRNA/mRNA interaction network was predicated for this circRNA. Subsequent mechanistic experiments showed that downregulation of circPAN3 could decrease the expression of X-linked inhibitor of apoptosis protein (XIAP), but this effect was counteracted by miR-153-3p or miR-183-5p specific inhibitors. Luciferase experiments further demonstrated that these molecules are involved in the circPAN3 regulatory network. Our results revealed that circPAN3 may be a key mediator for chemoresistance of AML cells, which may depend on the circPAN3-miR-153-5p/miR-183-5p-XIAP axis.
Drug Response:
resistant
Cancer basic information
Cancer:
acute myeloid leukemia
Tissue/Cell:
tissue and cell line (THP-1)
Other information
Title:
CircPAN3 mediates drug resistance in acute myeloid leukemia through the miR-153-5p/miR-183-5p-XIAP axis.
Journal:
Exp Hematol
Published:
2019
PubMed ID:
30395908