BackgroundDespite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor. There is therefore a strong need to identify potential molecular targets for the treatment of NSCLC. In the present study, we investigated the function of CPNE1 in the regulation of cell growth, migration and invasion.MethodsQuantitative real-time PCR (qRT-PCR) was used to detect the expression of CPNE1 and miR-335-5p. Western blot and immunohistochemical assays were used to investigate the levels of CPNE1 and other proteins. Flow cytometry was used to determine cell cycle stage and apoptosis. CCK-8 and clonogenic assays were used to investigate cell proliferation. Wound healing, migration and invasion assays were used to investigate the motility of cells. A lung carcinoma xenograft mouse model was used to investigate the in vivo effects of CPNE1 overexpression.ResultsWe observed that knockdown of CPNE1 and increased expression of miR-335-5p inhibits cell proliferation and motility in NSCLC cells, and found that CPNE1 was a target of miR-335-5p. In addition, our data indicated that CPNE1 inhibition could improve the clinical effects of EGFR-tyrosine kinase inhibitors.ConclusionsThe present results indicate that CPNE1 may be a promising molecular target in the treatment of NSCLC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0811-6) contains supplementary material, which is available to authorized users.
Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients is poor. Further understanding of the disease mechanism and treatment strategies is required. Copines are a family of calcium-dependent phospholipid-binding proteins that are evolutionally conserved in various eukaryotic organisms and protists. Copine 1, encoded by CPNE1, is a soluble membrane-binding protein, which includes two tandem C2 domains at the N-terminus and an A domain at the C-terminus. A previous study reported that Copine 1 binds with various intracellular proteins via its A domain and C omain. However, the role of CPNE1 in lung cancer remains unclear. In the presented study, CPNE1 expression level was demonstrated to be positively associated with the stage (P=0.002) and significantly associated with lymph node status (P=0.011) and distant metastasis (P=0.042). Furthermore, the function of CPNE1 in regulation of cell growth, migration and invasion was investigated, and it was demonstrated that knockdown of CPNE1 inhibits the cell cycle in NSCLC cells. Collectively, these data suggest that CPNE1 is an oncogene in NSCLC and serves an important role in tumorigenesis of NSCLC progression.
Wnt signal pathway genes are known to be involved with cancer development. Here we tested the hypothesis whether DNA methylation of genes part of the Wnt signaling pathway could help the diagnosis of non-small cell lung cancer (NSCLC). The methylation levels of SFRP1, SFRP2, WIF1 and PRKCB in 111 NSCLC patients were evaluated by quantitative methylation-specific PCR (qMSP). Promoter methylation levels of four candidate genes were significantly higher in tumor tissues compared with the adjacent tissues. SFRP1, SFRP2 and PRKCB genes were all shown to be good predictors of NSCLC risk (SFRP1: AUC = 0.711; SFRP2: AUC = 0.631; PRKCB: AUC = 0.650). The combined analysis showed that the methylation status of the four genes had a sensitivity of 70.3% and a specificity of 73.9% in the prediction of NSCLC risk for study cohort. A higher diagnostic value with an AUC of 0.945 (95% CI: 0.923–0.967, sensitivity: 90.6%, specificity: 93.0%) was found in TCGA cohort. In addition, SFRP1 and SFRP2 hypermethylation events were specific to male patients. Further TCGA data mining analysis suggested that SFRP1_cg15839448, SFRP2_cg05774801, and WIF1_cg21383810 were inversely associated with the host gene expression. Moreover, GEO database analysis showed that 5′-Aza-deoxycytidine was able to upregulate gene expression in several lung cancer cell lines. Subsequent dual-luciferase reporter assay showed a crucial regulatory function of PRKCB promoter. In summary, our study showed that a panel of Wnt signal pathway genes (SFRP1, SFRP2, WIF1 and PRKCB) had the potential as methylation biomarkers in the diagnosis of NSCLC.
Abstract. Aberrant DNA methylation is associated with non-small cell lung cancer (NSCLC), suggesting that gene promoter methylation may be a potential biomarker for the detection or risk prediction of NSCLC. The present study aimed to evaluate the potential usage of angiotensin II receptor type 1 (AGTR1) methylation in two major pathologic subtypes: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Quantitative methylation-specific polymerase chain reaction was used to investigate the effect of AGTR1 promoter methylation in the tumor and the paired adjacent non-tumor tissue samples from 42 patients with LUSC, and 69 with LUAD. The percentage of methylated reference was calculated and presented as the median (interquartile range 25th-75th percentile). The results of the current study revealed that there was significantly increased AGTR1 promoter methylation in the tumor tissues compared with the paired adjacent non-tumor tissue [97.4 (57.22-130.5) vs. 85 (48.25-123); P=0.024]. Furthermore, higher AGTR1 promoter methylation was observed in patients with LUSC compared with LUAD (odds ratio=2.483; 95% confidence interval=1.125-5.480; P=0.023). Significant differences were identified in AGTR1 methylation between non-tumor and the tumor tissues in LUSC [113.5 (68.33-148.73) vs. 93.04 (45.94-140); P=0.008]. In addition, the Cancer Genome Atlas data of 378 patients with LUSC and 477 with LUAD revealed an inverse correlation between gene expression and the methylation status of AGTR1 promoter.. These data suggest that AGTR1 hypermethylation is a promising biomarker to assist in LUSC detection and diagnosis. IntroductionLung cancer is a kind of malignancy that arises from epithelial cells. It is the leading cause of cancer-related death worldwide (1). There were nearly 1.8 million new patients and caused 159 million deaths in 2012, of which China accounted for more than one third (2). According to the size and appearance of the malignant cells, lung cancer is categorized as non small cell lung cancer (NSCLC) and small cell lung cancer (3). NSCLC represents approximately 85% of lung cancer (4), and it can be further subdivided into large cell carcinoma, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). There are a lot of differences in molecular profiling, characteristics and therapeutic methods between LUAD and LUSC (5).Promoter hypermethylation of the tumor suppressor genes has been recognized as an important factor in inducing oncogenesis (6). For example, SRY-box 17 (SOX17) methylation was found in 60.2% of primary lung cancer samples, and promoter methylation of SOX17 silenced gene expression, leading to the elimination of cell proliferation suppression in lung cancer (7). Identification of specific gene hypermethylation may explain the genomic instability and complexity of NSCLC and provide a basis for targeted therapy or risk prediction. AGTR1 promoter hypermethylation in lung squamouscell carcinoma but not in lung adenocarcinoma
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.