4.3 Article

MiR-200b regulates autophagy associated with chemoresistance in human lung adenocarcinoma

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

  1. National Natural Science Foundation of China [81071806, 81172106, 81301914, 81301913]
  2. Natural Science Foundation of Jiangsu Province [BK.2012371, BK20130698]

向作者/读者索取更多资源

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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