Long non-coding RNA UCA1 induces non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway in EGFR-mutant non-small cell lung cancer.

Content Provider	Europe PMC
Author	Cheng, Ningning Cai, Weijing Ren, Shengxiang Li, Xuefei Wang, Qi Pan, Hui Zhao, Mingchuan Li, Jiayu Zhang, Yishi Zhao, Chao Chen, Xiaoxia Fei, Ke Zhou, Caicun Hirsch, Fred R.
Copyright Year	2015
Abstract	The aim of this study was to explore the role of long non-coding RNA UCA1 (urothelial cancer-associated 1) in acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). In our study, UCA1 expression was significantly increased in lung cancer cells and patients with acquired resistance to EGFR-TKIs. Over-expression of UCA1 was significantly associated with a shorter progression-free survival (PFS) [13.0 vs. 8.5 months, P < 0.01] in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (10.5 vs. 12.0 months, P = 0.778), but in patients with non-T790M (19.0 vs. 9.0 months, P = 0.023). UCA1 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the AKT/mTOR pathway and epithelial-mesenchymal transition (EMT). The mTOR inhibitor was effective in UCA1-expressing cell PC9/R. Inhibiting mTOR could change the expression of UCA1, although there was no significant difference. In conclusion, the influence of over-expression of UCA1 on PFS for patients with acquired resistance to EGFR-TKIs was from the subgroup with non-T790M mutation. UCA1 may induce non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway and EMT.
Journal	Oncotarget
Volume Number	6
PubMed Central reference number	PMC4695138
Issue Number	27
PubMed reference number	26160838
e-ISSN	19492553
DOI	10.18632/oncotarget.4361
Language	English
Publisher	Impact Journals LLC
Publisher Date	2015-09-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2015 Cheng et al.
Subject Keyword	UCA1 EGFR-TKIs acquired resistance non-small cell lung cancer
Content Type	Text
Resource Type	Article
Subject	Oncology