Basic Information
Regular Relationship :
Tissue/Cell lineK562/ADR cells
SpecieHomo sapiens (human)
CitationPeerJ. 2021 May 25;9:e11429. doi: 10.7717/peerj.11429. eCollection 2021.
Reference title
Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR.
Experimental verification
CCK-8 assay;qRT-PCR;RNA sequencing;
Functional description
BACKGROUND: 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. METHODS: 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. RESULTS: 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(50)) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC(50) of doxorubicin. CONCLUSIONS: 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.
Annotations
External Annotation for CCDC26 |
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LncRNA-associated competing triplets and functions. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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Infer genomic variations that disturb lncRNA-associated ceRNA regulation.. |
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Provide and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. |
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Providing cellular-specific lncRNA-associated ceRNA networks predicted via high-throughput analysis of single-cell genomic data. |
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Information on all annotated and predicted human genes. |
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Gene nomenclature, gene families and associated resources (genomic, proteomic, phenotypic information). |
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Genome browser for vertebrate genomes. |
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An annotated collection of all publicly available DNA sequences. |
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A wiki-based platform for community curation of human long non-coding RNAs. |
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An integrated knowledge database dedicated to non-coding RNAs. |
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An integrated database of human annotated lncRNA transcripts. |
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Comprehensive annotations of eukaryotic long non-coding RNAs. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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A comprehensive, authoritative compendium of human genes and genetic phenotypes. |
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The catalogue of somatic mutations in cancer. |
