期刊
ONCOTARGET
卷 6, 期 32, 页码 32805-32820出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5352
关键词
miR-200b; autophagy; chemoresistance; human lung adenocarcinoma; ATG12
资金
- National Natural Science Foundation of China [81071806, 81172106, 81301914, 81301913]
- Natural Science Foundation of Jiangsu Province [BK.2012371, BK20130698]
Chemoresistance remains a major clinical problem in combating human lung adenocarcinoma (LAD), and abnormal autophagy is closely associated with this phenomenon. In the present study, an inverse correlation between miR-200b and autophagy-associated gene 12 (ATG12) expressions was observed in docetaxel-resistant (SPC-A1/DTX and H1299/DTX) and sensitive (SPC-A1 and H1299) LAD cells as well as in tissue samples. Further study showed that miR-200b directly targeted ATG12 in LAD. Moreover, miR-200b-dependent ATG12 downregulation inhibited autophagy and enhanced the chemosensitivity of SPC-A1/DTX and H1299/DTX cells both in vivo and in vitro. LAD chemoresistance is therefore closely related to downregulation of miR-200b and the corresponding upregulation of ATG12. These results provide new evidence for the mechanisms governing the microRNA (miRNA)-ATG12 network and their possible contribution to autophagy modulation and LAD chemoresistance.
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