Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun 130021, China.
FEBS Lett. 2013 Mar 1;587(5):436-43. doi: 10.1016/j.febslet.2012.12.027. Epub 2013 Jan 18.
Autophagy is a self-degrading process that is triggered by diverse stimuli including ionizing radiation. In this study we show novel phenomena in which transfection of miR-199a-5p mimic significantly suppresses IR-induced autophagy in MCF7 cells, and up-regulates basal and IR-induced autophagy in MDA-MB-231 breast cancer cells. We also identify DRAM1 and Beclin1 as novel target genes for miR-199a-5p. Overexpression of miR-199a-5p inhibits DRAM1 and Beclin1 expression in MCF7 cells, while it enhances expression of these genes in MDA-MB-231 cells. Furthermore, we show that miR-199a-5p sensitizes MDA-MB-231 cells to irradiation. Therefore, our data identify miR-199a-5p as a novel and unique regulator of autophagy, which plays an important role in cancer biology and cancer therapy.
自噬是一种自我降解的过程,由多种刺激物触发,包括电离辐射。在这项研究中,我们发现了新的现象,即转染 miR-199a-5p 模拟物可显著抑制 MCF7 细胞中 IR 诱导的自噬,并上调 MDA-MB-231 乳腺癌细胞中基础和 IR 诱导的自噬。我们还鉴定出 DRAM1 和 Beclin1 是 miR-199a-5p 的新靶基因。miR-199a-5p 的过表达抑制 MCF7 细胞中 DRAM1 和 Beclin1 的表达,而增强 MDA-MB-231 细胞中这些基因的表达。此外,我们表明 miR-199a-5p 使 MDA-MB-231 细胞对辐射敏感。因此,我们的数据确定 miR-199a-5p 是自噬的一种新的、独特的调节剂,在癌症生物学和癌症治疗中发挥重要作用。