Long Non-Coding RNA UCA1 Modulates Paclitaxel Resistance in Breast Cancer via miR-613/CDK12 Axis
Authors Liu C, Jiang F, Zhang X, Xu X
Received 11 December 2019
Accepted for publication 2 April 2020
Published 23 April 2020 Volume 2020:12 Pages 2777—2788
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Eileen O'Reilly
Chunhong Liu,1,* Feng Jiang,2,* Xueqin Zhang,3 Xiulong Xu1
1Department of Chinese Medicine, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong, People’s Republic of China; 2Department of Pharmacy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People’s Republic of China; 3Department of Internal Medicine, Shenxian Hospital of Traditional Chinese Medicine, Liaocheng, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiulong Xu
Department of Chinese Medicine, Yantai Hospital of Traditional Chinese Medicine, Yantai City, Shandong Province 264000, People’s Republic of China
Background: Paclitaxel (PTX) occupies a considerable status in the chemotherapies of breast cancer (BC), but the drug resistance keeps an obstructive factor of PTX treatment. This study was designed to explore the molecular mechanism of long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in PTX resistance of BC.
Methods: UCA1, microRNA-613 (miR-613) and cyclin-dependent kinase 12 (CDK12) expression was assayed through quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay was implemented for evaluating the half inhibitory concentrations (IC50) of PTX and cell viability. Cell apoptosis was examined by flow cytometry. The target relationship was explored using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. CDK12 protein level was detected through Western blot. Xenograft tumor assay was applied for assessing the influence of UCA1 on PTX resistance of BC in vivo.
Results: UCA1 expressed highly in PTX-resistant BC tissues and cells and regulated PTX resistance in BC cells by affecting cell viability and apoptosis in part. UCA1 negatively interacted with miR-613 and modulated PTX resistance via sponging miR-613. CDK12 was a downstream gene of miR-613 and miR-613 exerted the modulation of PTX resistance via targeting CDK12. Furthermore, UCA1 regulated CDK12 level through interacting with miR-613. The regulatory role of UCA1 in PTX resistance of BC was achieved by miR-613/CDK12 axis in vivo.
Conclusion: UCA1 mediated PTX resistance in BC through the miR-613/CDK12 axis, manifesting that UCA1 might improve the PTX treatment of BC as a significant therapeutic biomarker.
Keywords: UCA1, paclitaxel resistance, breast cancer, miR-613, CDK12
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]