期刊
ONCOTARGETS AND THERAPY
卷 13, 期 -, 页码 2783-2793出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S232769
关键词
long non-coding RNA; SPRY4-IT1; cisplatin resistance; MPZL-1; EMT
资金
- National Natural Science Foundation of China [81672307, 81501980, 81871871]
- Medical Innovation Team Foundation of the Jiangsu Provincial Enhancement Health Project [CXTDA2017021]
- 333 high class Talented Man Project [2016-II-426]
- Jiangsu Provincial Six Talent Peaks [WSW-264]
- Education and Health Medicine Innovation Team Project [CXTDA2017042]
- Nanjing Science and Technology Development Project [2017sc512046]
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.
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