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

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 docetax...

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Veröffentlicht in:Oncotarget 2015-10, Vol.6 (32), p.32805-32820
Hauptverfasser: Pan, Banzhou, Feng, Bing, Chen, Yitian, Huang, Guichun, Wang, Rui, Chen, Longbang, Song, Haizhu
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Sprache:eng
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Zusammenfassung: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.5352