MicroRNA-33b regulates sensitivity to daunorubicin in acute myelocytic leukemia by regulating eukaryotic translation initiation factor 5A-2
| Autor: | Wei Chen, Xiling Lu, Fengchang Bao, Pingchong Lei, Cheng Lian, Yao Li, Yanhui Liu, Kai Sun, Fei Xue, Runhong Yu, Hong Qiao |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Daunorubicin Cell Survival Blotting Western Antineoplastic Agents Apoptosis HL-60 Cells Biochemistry Flow cytometry 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation RNA interference Peptide Initiation Factors hemic and lymphatic diseases Cell Line Tumor microRNA medicine Biomarkers Tumor Gene silencing Humans Viability assay Molecular Biology Cell Proliferation Gene knockdown medicine.diagnostic_test Chemistry Gene Expression Regulation Leukemic Gene Expression Profiling RNA-Binding Proteins Cell Biology Flow Cytometry Leukemia Myeloid Acute MicroRNAs 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research medicine.drug |
| Zdroj: | Journal of cellular biochemistry. 121(1) |
| ISSN: | 1097-4644 |
| Popis: | In this study, we aimed to study the effect of miR-33b in regulating sensitivity to daunorubicin (DNR) in acute myelocytic leukemia (AML). We used quantitative real-time polymerase chain reaction and Cell Counting Kit-8 assay to detect the level of miR-33b and cell viability. Cell apoptosis and the expression of eIF5A-2 and MCL-1 protein were detected by flow cytometry analysis and Western Blot analysis, respectively. MiR-33b mimic increased sensitivity of AML cells against DNR, while miR-33b inhibitor had the opposite effect. Furthermore, the results showed that the eIF5A-2 gene was a direct target of miR-33b, and miR-33b regulated eIF5A-2 mRNA and protein expression. Silencing of eIF5A-2 by RNA interference increased the sensitivity of AML cells against DNR. We also found that MCL-1 contributed to the regulation of DNR sensitivity, which was dependent on downregulation of eIF5A-2. Finally, knockdown of eIF5A-2 eliminated the effects of miRNA-33b mimic or inhibitor on DNR sensitivity. These findings indicate that miR-33b maybe as a new therapeutic target in AML cells. |
| Databáze: | OpenAIRE |
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