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

Autor: Jingyao Gu, Yunyao Ye, Lihua Jiang, Shanxun Yu, He Wang, Gaohua Han, Tianyao Lei, Pei Liu, Zhaoxia Wang
Rok vydání: 2020
Předmět:
Zdroj: OncoTargets and Therapy. 13:2783-2793
ISSN: 1178-6930
DOI: 10.2147/ott.s232769
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje