Back to Journals » OncoTargets and Therapy » Volume 13

Long Non-Coding RNA SPRY4-IT1 Reverses Cisplatin Resistance by Downregulating MPZL-1 via Suppressing EMT in NSCLC

Authors Ye Y, Gu J, Liu P, Wang H, Jiang L, Lei T, Yu S, Han G, Wang Z

Received 2 October 2019

Accepted for publication 8 March 2020

Published 2 April 2020 Volume 2020:13 Pages 2783—2793

DOI https://doi.org/10.2147/OTT.S232769

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Yunyao Ye,1,2,* Jingyao Gu,1,* Pei Liu,1,3,* He Wang,1,4 Lihua Jiang,1 Tianyao Lei,1 Shanxun Yu,2 Gaohua Han,2 Zhaoxia Wang1

1Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Oncology, Taizhou People’s Hospital, Taizhou, Jiangsu, People’s Republic of China; 3Department of Digestive Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Oncology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhaoxia Wang
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People’s Republic of China
Tel +86-25-58509810
Fax +86-25-58509994
Email zhaoxiawang66@126.com

Purpose: Long non-coding RNA (lncRNA) SPRY4 intronic transcript 1 (SPRY4-IT1) is reported to play important roles in the occurrence and development of many tumors. However, the possible role of SPRY4-IT1 in cisplatin (DDP) resistance of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study is to investigate the functions and molecular mechanisms underlying SPRY4-IT1 of cisplatin resistance in NSCLC.
Methods: Expression of SPRY4-IT1 was analyzed in A549 and cisplatin-resistant A549/DDP cell lines by quantitative real-time polymerase chain reaction (RT-qPCR). Overexpression techniques were applied to investigate the biological functions of SPRY4-IT1 in cisplatin-resistant A549/DDP cells. The effects of SPRY4-IT1 on proliferation and apoptosis were evaluated using cell counting kit-8 (CCK8) assays, colony formation assay and flow-cytometric analysis. The expressions of epithelial–mesenchymal transition (EMT)-associated proteins, including E-cadherin and Vimentin, were detected by Western blot. Microarray analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by Western blotting and RT-qPCR. A549/DDP cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice in order to verify the effect of SPRY4-IT1 on cisplatin resistance in vivo.
Results: The present study demonstrated that SPRY4-IT1 expression was decreased in A549/DDP cells compared with parental A549 cells. Upregulation of SPRY4-IT1 suppressed cell proliferation and caused apoptosis of A549/DDP cells both in vitro and in vivo. MPZL-1 was negatively regulated by SPRY4-IT1. Furthermore, upregulation of SPRY4-IT1 and downregulation of MPZL-1 could suppress epithelial–mesenchymal transition (EMT), which was characterized by increased E-cadherin expression and decreased Vimentin expression.
Conclusion: Upregulation of SPRY4-IT1 reversed the cisplatin-resistant phenotype of NSCLC partially by downregulating MPZL-1 via inhibiting EMT process.

Keywords: long non-coding RNA, SPRY4-IT1, cisplatin resistance, MPZL-1, EMT

Creative Commons License 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]