Depleting PTOV1 sensitizes non-small cell lung cancer cells to chemotherapy through attenuating cancer stem cell traits

Abstract

Background Prostate 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). Methods The 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. Results PTOV1 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. Conclusion These 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. Electronic supplementary material The online version of this article (10.1186/s13046-019-1349-y) contains supplementary material, which is available to authorized users.

Investigating the effects of chronic perinatal alcohol and combined nicotine and alcohol exposure on dopaminergic and non-dopaminergic neurons in the VTA

“…PTOV1 gene was significantly differentially upregulated (p < 0.001) in the DA neurons following both perinatal exposure groups and not significantly expressed in non-DA neurons. Significant overexpression of PTOV1 has been suggested to exhibit an anti-cancer effect when knockdown 94 – 97 . Synaptogyrin 3 (SYNGR3) was only significantly upregulated in the nicotine-alcohol DA group (p < 0.001).…”

STAT3/miR-135b/NF-κB axis confers aggressiveness and unfavorable prognosis in non-small-cell lung cancer

“…4 × 10 4 cells were seeded on coverslips (Thermo Fisher Scientific, USA) in 24-well plates overnight. Cells were treated with TNF-α (10 ng/ml) for 20 min and then stained as previously described 51 . Primary antibody against NF-κB p65 (1:100, sc-8008, Santa Cruz, USA) and TRITC-conjugated secondary antibody (1:500; Jackson Immuno-Research Laboratories, USA) were used.…”

PTOV1 is a Prognostic Biomarker and Correlated with Poor Progression in Colorectal Cancer

“…Likewise, other studies show that PTOV1 promotes prostate cancer invasion and growth by counteracting Notch pathway signaling and promoting the translation of JUN (encoding C-Jun) [8]. Moreover, more and more studies showed that PTOV1 as a prognostic factor for patients with many cancers such as ovarian cancer, nonsmall cell lung cancer, urothelial carcinoma and other cancer [9][10][11][12]. And also, PTOV1 might be a target for inhibition of chemotherapy resistance [9,10,13].…”