Abstract
BackgroundProstate tumor over expressed gene 1 (PTOV1) has been reported as an oncogene in several human cancers. However, the clinical significance and biological role of PTOV1 remain elusive in non-small cell lung cancer (NSCLC).MethodsThe Cancer Genome Atlas (TCGA) data and NCBI/GEO data mining, western blotting analysis and immunohistochemistry were employed to characterize the expression of PTOV1 in NSCLC cell lines and tissues. The clinical significance of PTOV1 in NSCLC was studied by immunohistochemistry statistical analysis and Kaplan–Meier Plotter database mining. A series of in-vivo and in-vitro assays, including colony formation, CCK-8 assays, flow cytometry, wound healing, trans-well assay, tumor sphere formation, quantitative PCR, gene set enrichment analysis (GSEA), immunostaining and xenografts tumor model, were performed to demonstrate the effects of PTOV1 on chemosensitivity of NSCLC cells and the underlying mechanisms.ResultsPTOV1 is overexpressed in NSCLC cell lines and tissues. High PTOV1 level indicates a short survival time and poor response to chemotherapy of NSCLC patients. Depleting PTOV1 increased sensitivity to chemotherapy drugs cisplatin and docetaxel by increasing cell apoptosis, inhibiting cell migration and invasion. Our study verified that depleting PTOV1 attenuated cancer stem cell traits through impairing DKK1/β-catenin signaling to enhance chemosensitivity of NSCLC cells.ConclusionThese results suggest that PTOV1 plays an important role in the development and progression of human NSCLC and PTOV1 may serve as a therapeutic target for NSCLC patients.
Highlights
Prostate tumor over expressed gene 1 (PTOV1) has been reported as an oncogene in several human cancers
PTOV1 is significantly upregulated in non-small cell lung cancer (NSCLC) PTOV1 was reported to be upregulated in kinds of cancer, there is no systematic analysis of the expression of PTOV1 in NSCLC
Data from the The Cancer Genome Atlas (TCGA) database showed that PTOV1 levels were dramatically increased in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues as compared to the normal
Summary
Prostate tumor over expressed gene 1 (PTOV1) has been reported as an oncogene in several human cancers. The clinical significance and biological role of PTOV1 remain elusive in non-small cell lung cancer (NSCLC). Cancer stem cells (CSCs) are tumor cells that possess the principal properties of self-renewal, clonal tumor. CSCs have been reported in most types of human cancers, including NSCLC. It was reported that CD133+ lung cancer cells represented the cancer stem cell population, which were able to grow indefinitely as tumor spheres in serum-free medium containing EGF and bFGF and tumorigenic [8]. Expression of pluripotency factors, such as Oct and Nanog, proved to enhance lung cancer stem-like properties [9, 10]. Giulia Bertolini et al reported that lung cancer CD133+ cells display stem-like features and resistant to cisplatin [13].
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