Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Drug resistance is the main obstacle in the treatment of leukemia. As a member of the competitive endogenous RNA (ceRNA) mechanism, underlying roles of lncRNA are rarely reported in drug-resistant leukemia cells. The gene expression profiles of lncRNAs and mRNAs in doxorubicin-resistant K562/ADR and...

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Bibliographic Details
Published in:PeerJ (San Francisco, CA) Vol. 9; p. e11429
Main Authors: Liu, Zhaoping, Wang, Yanyan, Xu, Zhenru, Yuan, Shunling, Ou, Yanglin, Luo, Zeyu, Wen, Feng, Liu, Jing, Zhang, Ji
Format: Journal Article
Language:English
Published: United States PeerJ. Ltd 25-05-2021
PeerJ, Inc
PeerJ Inc
Subjects:
Analysis
Anthracyclines
Bioinformatics
Cancer
Cell Biology
Cell survival
ceRNA network
Cholecystokinin
Dasatinib
Doxorubicin
Drug resistance
Drug therapy
Drugs and Devices
Gene expression
Genes
Genetic aspects
Leukemia
Long non-coding RNA
Messenger RNA
MicroRNA
MicroRNAs
miRNA
Molecular Biology
Pharmacology
RNA sequencing
siRNA
Software
Therapeutic targets
Transfection
Vincristine
United States > US
China
ceRNA network
Drug resistance
Bioinformatics
Leukemia
Long non-coding RNA
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Summary:Drug resistance is the main obstacle in the treatment of leukemia. As a member of the competitive endogenous RNA (ceRNA) mechanism, underlying roles of lncRNA are rarely reported in drug-resistant leukemia cells. The gene expression profiles of lncRNAs and mRNAs in doxorubicin-resistant K562/ADR and sensitive K562 cells were established by RNA sequencing (RNA-seq). Expression of differentially expressed lncRNAs (DElncRNAs) and DEmRNAs was validated by qRT-PCR. The potential biological functions of DElncRNAs targets were identified by GO and KEGG pathway enrichment analyses, and the lncRNA-miRNA-mRNA ceRNA network was further constructed. K562/ADR cells were transfected with CCDC26 and LINC01515 siRNAs to detect the mRNA levels of GLRX5 and DICER1, respectively. The cell survival rate after transfection was detected by CCK-8 assay. The ceRNA network was composed of 409 lncRNA-miRNA pairs and 306 miRNA-mRNA pairs based on 67 DElncRNAs, 58 DEmiRNAs and 192 DEmRNAs. Knockdown of CCDC26 and LINC01515 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the half-maximal inhibitory concentration (IC ) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC of doxorubicin. The ceRNA regulatory networks may play important roles in drug resistance of leukemia cells. CCDC26/miR-140-5p/GLRX5 and LINC01515/miR-425-5p/DICER1 may be potential targets for drug resistance in K562/ADR cells. This study provides a promising strategy to overcome drug resistance and deepens the understanding of the ceRNA regulatory mechanism related to drug resistance in CML cells.
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ISSN:2167-8359
2167-8359
DOI:10.7717/peerj.11429