4.7 Article Retracted Publication

被撤回的出版物: The miR 495-UBE2C-ABCG2/ERCC1 axis reverses cisplatin resistance by downregulating drug resistance genes in cisplatin-resistant non-small cell lung cancer cells (Retracted article. See vol. 63, 2021)

期刊

EBIOMEDICINE
卷 35, 期 -, 页码 204-221

出版社

ELSEVIER
DOI: 10.1016/j.ebiom.2018.08.001

关键词

MicroRNA-495; UBE2C; ABCG2; ERCC1; EMT; Cisplatin resistant

资金

  1. National Natural Science Foundation of China [3180108]
  2. Science and Technology Development Foundation of Yantai [2015ZH082]
  3. Natural Science Foundation of Shandong Province [ZR2018QH004, ZR2016HB55, ZR2017PH067, ZR2017PH028]
  4. Research Foundation of Binzhou Medical University [BY2015KYQD25, BY2015KJ14]

向作者/读者索取更多资源

Cisplatin (DDP) resistance has become the leading cause of mortality in non-small cell lung cancer (NSCLC). miRNA dysregulation significantly contributes to tumor progression. In this study, we found that miR-495 was significantly downregulated in lung cancer tissue specimens. This study aimed to elucidate the functions, direct target genes, and molecular mechanisms of miR-495 in lung cancer. miR-495 downregulated its substrate UBE2C through direct interaction with UBE2C 3'- untranslated region. UBE2C is a proto-oncogene activated in lung cancer; however, its role in chemotherapeutic resistance is unclear. Herein, UBE2C expression levels were higher in DDP-resistant NSCLC cells; this was associated with the proliferation, invasion, and DDP resistance in induced cisplatin-resistant NSCLC cells. Furthermore, epithelial-mesenchymal transitions (EMT) contributed to DDP resistance. Moreover, UBE2C knockdown downregulated vimentin. In contrast, E-cadherin was upregulated. Importantly, miR-495 and UBE2C were associated with cisplatin resistance. We attempted to evaluate their effects on cell proliferation and cisplatin resistance. We also performed EMT, cell migration, and invasion assays in DDP-resistant NSCLC cells overexpressing miR-495 and under-expressing UBE2C. Furthermore, in silico assays coupled with western blotting and luciferase assays revealed that UBE2C directly binds to the 5'-UTR of the drugresistance genes ABCG2 and ERCC1. Furthermore, miR-495 downregulated ABCG2 and ERCCI via regulation of UBE2C. Together, the present results indicate that the miR495-UBE2C-AJ3CG2/ERCC1 axis reverses DDP resistance via downregulation of anti-drug genes and reducing EMT in DDP-resistant NSCLC cells. (C) 2018 The Author(s). Published by Elsevier B.V.

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