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

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机构: [1]Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China [2]Department of Clinical Laboratory, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China [3]Department of Clinical Laboratory, The Second Affiliated Hospital, Hainan Medical University, Haikou, Hainan, China [4]Department of Hematology, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China [5]Molecular Biology Research Center & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
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关键词: Long non-coding RNA ceRNA network Drug resistance Bioinformatics Leukemia

摘要:
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 (IC50) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC50 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.© 2021 Liu et al.

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出版当年[2020]版:
大类 | 3 区 生物
小类 | 3 区 综合性期刊
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 综合性期刊
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出版当年[2019]版:
Q2 MULTIDISCIPLINARY SCIENCES
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Q2 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China [2]Department of Clinical Laboratory, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China
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通讯机构: [1]Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China [2]Department of Clinical Laboratory, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China
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