AUTHOR=Tang Huaping , Chen Jianyou , Han Xiaolei , Feng Yan , Wang Fang 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.646390

DOI=10.3389/fcell.2021.646390

ISSN=2296-634X

ABSTRACT=<p>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 (<italic>SPP1</italic>) 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 <italic>SPP1</italic> in tumor tissues was significantly higher than normal tissues. The high expression of <italic>SPP1</italic> was also correlated with tumor grade and poor clinical prognosis. To understand the roles of <italic>SPP1</italic> and the DNA methyltransferase 1 (<italic>DNMT1</italic>), which regulated <italic>SPP1</italic> expression, in affecting cell viability, migration and invasion, <italic>SPP1</italic> and <italic>DNMT1</italic> were overexpressed in the human lung cancer A549 and NCI-446 cells, followed by analyzing cell viability, migration and invasion. We showed that <italic>SPP1</italic> promoted the proliferation, migration and invasion of lung cancer cells, and increased the resistance of lung cancer to the chemotherapeutic drug cisplatin. Knocking down <italic>SPP1</italic> in cells restored sensitivity to cisplatin. Further, A549 cells without <italic>SPP1</italic> overexpression demonstrated lower tumor growth rate than <italic>SPP1</italic> overexpression cells using the xenograft tumor mouse model. High expression of <italic>SPP1</italic> in lung cancer tumor tissue was caused by the reduced methylation level of its promoter region mediated by <italic>DNMT1</italic>. Our data suggested that <italic>SPP1</italic> can be used as a marker for highly malignant lung cancer and targeting <italic>SPP1</italic> may be a potential lung cancer treatment strategy.</p>