Depleting PTOV1 sensitizes non-small cell lung cancer cells to chemotherapy through attenuating cancer stem cell traits
Depleting PTOV1 sensitizes non-small cell lung cancer cells to chemotherapy through attenuating cancer stem cell traits
复制标题
消除 PTOV1 通过减弱癌症干细胞特性使非小细胞肺癌细胞对化疗敏感
DOI：
10.1186/s13046-019-1349-y
复制
发表时间：
2019-08-06
影响因子：
11.3
通讯作者：
Yuan, Zhiyong
中科院分区：
文献类型：
--
作者：
Wu, Zhiqiang;Liu, Zhuang;Yuan, Zhiyong
背景前列腺肿瘤过度表达基因 1 (PTOV1) 已被报道为多种人类癌症的癌基因。然而，PTOV1在非小细胞肺癌（NSCLC）中的临床意义和生物学作用仍不清楚。方法采用癌症基因组图谱（TCGA）数据和NCBI/GEO数据挖掘、蛋白质印迹分析和免疫组织化学来表征PTOV1在NSCLC细胞系和组织中的表达。通过免疫组织化学统计分析和Kaplan-Meier Plotter数据库挖掘研究PTOV1在NSCLC中的临床意义。通过一系列体内外实验，包括集落形成、CCK-8实验、流式细胞术、伤口愈合、跨孔实验、肿瘤球形成、定量PCR、基因集富集分析（GSEA）、免疫染色和异种移植肿瘤模型，论证PTOV1对NSCLC细胞化疗敏感性的影响及其潜在机制。结果PTOV1在NSCLC细胞系和组织中过表达。高 PTOV1 水平表明 NSCLC 患者的生存时间短且对化疗反应差。消除 PTOV1 通过增加细胞凋亡、抑制细胞迁移和侵袭来增加对化疗药物顺铂和多西紫杉醇的敏感性。我们的研究证实，消除 PTOV1 通过损害 DKK1/β-catenin 信号传导来增强 NSCLC 细胞的化疗敏感性，从而减弱癌症干细胞特性。结论这些结果表明 PTOV1 在人类 NSCLC 的发生和进展中发挥着重要作用，PTOV1 可能作为 NSCLC 患者的治疗靶点。
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.