scholarly journals Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1523
Author(s):  
Federico Pio Fabrizio ◽  
Angelo Sparaneo ◽  
Andrea Fontana ◽  
Tommaso Mazza ◽  
Paolo Graziano ◽  
...  

The silencing of SPARC (secreted protein acid and rich in cysteine) gene through methylation of its promoter region represents a common event in many solid tumors and it is frequently associated with tumor progression and an aggressive clinical outcome. Anyhow, the data concerning the epigenetic mechanism of SPARC deregulation and its prognostic value in lung cancer are still incomplete. We explored the aberrant methylation of SPARC and its effects in 4 non-small cell lung cancer (NSCLC) cell lines and 59 NSCLC tissues and correlated the methylation levels with clinical-pathological features and disease outcome of patients. In 3 out of 4 tumor cell lines high SPARC methylation levels were observed. An inverse correlation between the epigenetic silencing and SPARC expression was confirmed by 5-Aza-2′-deoxycytidine ((5-Aza-CdR) treatment that also significantly induced a reduction in cell viability, proliferation and tumor cell migration. In tissues, the DNA methylation levels of the SPARC gene were significantly lower in paired non-neoplastic lungs (NLs) and normal lungs distant from tumor (NLDTs) than in NSCLCs (p = 0.002 and p = 0.0034 respectively). A promoter hypermethylation was detected in 68% of squamous cell carcinoma (SqCCs, 17/25) and 56% of adenocarcinoma (ADCs, 19/34), with SqCC showing the highest levels of methylation. Higher SPARC methylation levels were significantly associated with higher mortality risk both in all NSCLCs early stage patients (Hazard Ratio, HR = 1.97; 95% Confidence Interval, CI: 1.32–2.93; p = 0.001) and in those with SqCC (HR = 2.96; 95% CI: 1.43–6.12; p = 0.003). Promoter methylation of SPARC gene should represent an interesting prognostic biomarker in NSCLC, with potential application in the squamous early-stage context. Further research in this setting on larger independent cohorts of lung patients with different histologies and stages of disease are warranted.

2019 ◽  
Vol 38 (4) ◽  
pp. 946-955
Author(s):  
Maximilian Hochmair ◽  
Barbara Rath ◽  
Lukas Klameth ◽  
Ernst Ulsperger ◽  
Christoph Weinlinger ◽  
...  

1990 ◽  
Vol 82 (4) ◽  
pp. 305-310 ◽  
Author(s):  
D. P. Bliss ◽  
J. F. Battey ◽  
R. I. Linnoila ◽  
M. J. Birrer ◽  
A. F. Gazdar ◽  
...  

1996 ◽  
Vol 63 (S24) ◽  
pp. 210-217 ◽  
Author(s):  
Bruce E. Johnson ◽  
Edward Russell ◽  
Alfreda M. Simmons ◽  
Ruby Phelps ◽  
Seth M. Steinberg ◽  
...  

2020 ◽  
Author(s):  
Dan Wang ◽  
Shufang Yu ◽  
Shasha Yi ◽  
Sichan Liu

Abstract Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumor, and its recurrence and metastasis are the main causes of death. Recently, there are evidences that tumor derived exosomes play an important role in the occurrence and development of non-small cell lung cancer.Material/Methods: First, miR-185-5p and RAB35 expression in tumor tissues, paracancerous healthy tissues, lung cancer cell lines and normal bronchial epithelial cell line were detected. Then, miR-185-5p and RAB35 were over-expressed/knocked down to study their effects on A549 cells and H2170 cells proliferation, migration and invasion . Next, bioinformatics analysis and luciferase reporter gene analysis verified the targeting relationships of miR-185-5p and RAB35 , respectively. Finally, the exosomes secreted by tumor cells with RAB35 gene downregulated or miR-185-5p overexpression were co cultured with their parent cells to verify the regulatory effect of RAB35 on the secretion and function of exosomes.Results: The miR-185-5p expression was downregulated, while RAB35 expression was prominently upregulated in NSCLC tissues and cell lines. Moreover, miR-185-5p overexpression or RAB35 downregulated suppressed cells proliferation, migration and invasion. Furthermore, we clarified that RAB35 was a direct target of miR-185-5p. Additionally, exosomes derived from tumor cells could restore cells proliferation, migration and invasion, while exosomes secreted by tumor cells with RAB35 downregulated or mR-185-5p overexpression lose the ability to restore cells proliferation, migration and invasion.Conclusions: Our findings indicate that miR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of NSCLC cells.


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