期刊
MOLECULAR ONCOLOGY
卷 15, 期 4, 页码 1203-1216出版社
WILEY
DOI: 10.1002/1878-0261.12661
关键词
acute myeloid leukemia; autophagy; cytarabine resistance; DANCR; long noncoding RNA; miR-874-3P/ATG16L1 axis
类别
资金
- Natural Science Foundation of Shandong Province, China [ZR2017LH029]
- PhD Research Foundation of Affiliated Hospital of Jining Medical University, China [2016-BS-001]
- Medicine and Health Science Technology Development Program of Shandong Province, China [2017WS514]
- Scientific Research Supported Foundation for the Young Teacher of Jining Medical University, China [JY2017FS008]
- Project of Scientific Research Program of Affiliated Hospital of Jining Medical University [MP-2016-007]
This study identifies DANCR as a positive regulator of Ara-C resistance in human AML cells, suggesting that this lncRNA may serve as a potential target for overcoming Ara-C resistance in AML chemotherapy by promoting MIR-874-3P/ATG16L1 axis-regulated autophagy.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据