Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance

• Published in: Frontiers in cell and developmental biology Vol. 9; p. 646390
• Main Authors: Tang, Huaping, Chen, Jianyou, Han, Xiaolei, Feng, Yan, Wang, Fang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29.04.2021
• Subjects: Cell and Developmental Biology; chemotherapeutic drug; cisplatin resistance; DNMT1; lung cancer; SPP1; lung cancer; SPP1; DNMT1; chemotherapeutic drug; cisplatin resistance
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.646390

The chemoresistance of lung cancer is a significant contributor to its high mortality and morbidity rate. There is an urgent need to identify differentially expressed genes in lung cancer patients with a poor prognosis to develop effective means to overcome drug resistance in subsequent treatment. In this study, we identified the secreted phosphoprotein 1 ( ) as a potential gene associated with a poor diagnosis of lung cancer patients using the Cancer Genome Atlas analysis, which suggested that the expression of in tumor tissues was significantly higher than normal tissues. The high expression of was also correlated with tumor grade and poor clinical prognosis. To understand the roles of and the DNA methyltransferase 1 ( ), which regulated expression, in affecting cell viability, migration and invasion, and were overexpressed in the human lung cancer A549 and NCI-446 cells, followed by analyzing cell viability, migration and invasion. We showed that promoted the proliferation, migration and invasion of lung cancer cells, and increased the resistance of lung cancer to the chemotherapeutic drug cisplatin. Knocking down in cells restored sensitivity to cisplatin. Further, A549 cells without overexpression demonstrated lower tumor growth rate than overexpression cells using the xenograft tumor mouse model. High expression of in lung cancer tumor tissue was caused by the reduced methylation level of its promoter region mediated by . Our data suggested that can be used as a marker for highly malignant lung cancer and targeting may be a potential lung cancer treatment strategy.