Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis
Autophagy is an important mechanism involved in the regulation of acute myeloid leukemia (AML) chemoresistance. The long noncoding RNA (lncRNA) differentiation antagonizing non‐protein coding RNA (DANCR) exhibits oncogenic activity in several types of human cancers, including AML, but it remains unc...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12661 |
| _version_ | 1818863534926200832 |
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| author | Hao Zhang Ling Liu Lulu Chen Haihui Liu Saisai Ren Yanling Tao |
| author_facet | Hao Zhang Ling Liu Lulu Chen Haihui Liu Saisai Ren Yanling Tao |
| author_sort | Hao Zhang |
| collection | DOAJ |
| description | Autophagy is an important mechanism involved in the regulation of acute myeloid leukemia (AML) chemoresistance. The long noncoding RNA (lncRNA) differentiation antagonizing non‐protein coding RNA (DANCR) exhibits oncogenic activity in several types of human cancers, including AML, but it remains unclear whether it regulates autophagy and chemoresistance in AML. We report here that cytarabine (Ara‐C) treatment elevates DANCR expression in human AML cells. In addition, DANCR overexpression confers and its knockdown diminishes Ara‐C resistance in human AML cells, suggesting that DANCR positively regulates AML chemoresistance to Ara‐C. Moreover, DANCR promotes autophagy in Ara‐C‐treated human AML cells and acts as a sponge to decrease miR‐20a‐5p expression, thereby upregulating the expression of ATG16L1, a critical component of the autophagy machinery. Importantly, ATG16L1 silencing abrogates DANCR‐promoted autophagy and markedly restores DANCR‐conferred Ara‐C resistance, suggesting that DANCR promotes MIR‐874‐3P/ATG16L1 axis‐regulated autophagy to confer Ara‐C resistance in human AML cells. Together, this study identifies DANCR as a positive regulator of Ara‐C resistance in human AML cells, suggesting this lncRNA as a potential target for overcoming Ara‐C resistance in AML chemotherapy. |
| first_indexed | 2024-12-19T10:17:18Z |
| format | Article |
| id | doaj.art-97a76830472e46b8b3848dc4999814c4 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-19T10:17:18Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-97a76830472e46b8b3848dc4999814c42022-12-21T20:26:11ZengWileyMolecular Oncology1574-78911878-02612021-04-011541203121610.1002/1878-0261.12661Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axisHao Zhang0Ling Liu1Lulu Chen2Haihui Liu3Saisai Ren4Yanling Tao5Department of Hematology Affiliated Hospital of Jining Medical University ChinaDepartment of Hematology Affiliated Hospital of Jining Medical University ChinaGraduate School Jining Medical University ChinaDepartment of Hematology Affiliated Hospital of Jining Medical University ChinaDepartment of Hematology Affiliated Hospital of Jining Medical University ChinaDepartment of Pediatric Hematology Affiliated Hospital of Jining Medical University ChinaAutophagy is an important mechanism involved in the regulation of acute myeloid leukemia (AML) chemoresistance. The long noncoding RNA (lncRNA) differentiation antagonizing non‐protein coding RNA (DANCR) exhibits oncogenic activity in several types of human cancers, including AML, but it remains unclear whether it regulates autophagy and chemoresistance in AML. We report here that cytarabine (Ara‐C) treatment elevates DANCR expression in human AML cells. In addition, DANCR overexpression confers and its knockdown diminishes Ara‐C resistance in human AML cells, suggesting that DANCR positively regulates AML chemoresistance to Ara‐C. Moreover, DANCR promotes autophagy in Ara‐C‐treated human AML cells and acts as a sponge to decrease miR‐20a‐5p expression, thereby upregulating the expression of ATG16L1, a critical component of the autophagy machinery. Importantly, ATG16L1 silencing abrogates DANCR‐promoted autophagy and markedly restores DANCR‐conferred Ara‐C resistance, suggesting that DANCR promotes MIR‐874‐3P/ATG16L1 axis‐regulated autophagy to confer Ara‐C resistance in human AML cells. Together, this study identifies DANCR as a positive regulator of Ara‐C resistance in human AML cells, suggesting this lncRNA as a potential target for overcoming Ara‐C resistance in AML chemotherapy.https://doi.org/10.1002/1878-0261.12661acute myeloid leukemiaautophagycytarabine resistanceDANCRlong noncoding RNAmiR‐874‐3P/ATG16L1 axis |
| spellingShingle | Hao Zhang Ling Liu Lulu Chen Haihui Liu Saisai Ren Yanling Tao Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis Molecular Oncology acute myeloid leukemia autophagy cytarabine resistance DANCR long noncoding RNA miR‐874‐3P/ATG16L1 axis |
| title | Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis |
| title_full | Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis |
| title_fullStr | Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis |
| title_full_unstemmed | Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis |
| title_short | Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis |
| title_sort | long noncoding rna dancr confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the mir 874 3p atg16l1 axis |
| topic | acute myeloid leukemia autophagy cytarabine resistance DANCR long noncoding RNA miR‐874‐3P/ATG16L1 axis |
| url | https://doi.org/10.1002/1878-0261.12661 |
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