The miR-290-295 cluster suppresses autophagic cell death of melanoma cells

被引：51

作者：

Yong Chen

Ruediger Liersch

Michael Detmar

机构：

[1] Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich

[2] Department of Medicine, Hematology and Oncology, University Hospital Muenster, Muenster

来源：

Scientific Reports | / 2卷 / 1期

基金：

欧洲研究理事会;

关键词：

D O I：

10.1038/srep00808

中图分类号：

学科分类号：

摘要：

We compared the expression levels of 307 miRNAs in six different B16F1 melanoma cell lines of differing malignant properties and found that the miR-290-295 cluster showed a strong upregulation in the more malignant B16F1 daughter cell lines. Its overexpression in B16F1 cells had no major effects on cell proliferation, migration or anchorage-independent growth, but conferred resistance to glucose starvation. This was mediated by miR-290-295-induced downregulation of several essential autophagy genes, including Atg7 and ULK1, which resulted in inhibition of autophagic cell death induced by glucose starvation. Similar effects were observed after knockdown of Atg7 or ULK1 in B16F1 melanoma cells, and after treatment with two chemical inhibitors of autophagy. Together, these results indicate that autophagy mediates cell death of melanoma cells under chronic nutrient deprivation, and they reveal an unanticipated role of the miR-290-295 cluster in conferring a survival advantage to melanoma cells by inhibiting autophagic cell death.

引用

共 40 条

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