MiR-200b regulates autophagy associated with chemoresistance in human lung adenocarcinoma
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Banzhou Pan1, Bing Feng1, Yitian Chen1, Guichun Huang1, Rui Wang1, Longbang Chen1,*, Haizhu Song1,*
1Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
*These authors have contributed equally to this work
Haizhu Song, e-mail: [email protected]
Keywords: miR-200b, autophagy, chemoresistance, human lung adenocarcinoma, ATG12
Received: April 12, 2015 Accepted: September 10, 2015 Published: September 21, 2015
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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