Relationship between DLK1 gene promoter region DNA methylation and non-small cell lung cancer biological behavior

BACKGROUND: Nuclear pore membrane protein 121 (POM121) is a novel biomarker involved in tumorigenesis and metastasis. However, little is known about the role of POM121 in non-small-cell lung cancer (NSCLC). OBJECTIVE: The aim of this study was to detect the expression of POM121 in NSCLC and its relationship with clinicopathologic feature and cell biological behavior, and explore the underlying mechanisms. METHODS: The expression of POM121 in NSCLC tissues and para-carcinoma tissues was compared by quantitative real-time PCR and immunohistochemistry analysis. The relationship between POM121 protein and clinicopathological characteristics in NSCLC was investigated. Roles of POM121 in NSCLC cells were investigated by CCK-8 assay, clone formation assay, transwell migration and invasion assay, and in vivo experiments. Variations of signaling pathways were determined by qRT-PCR and Western blot. RESULTS: The POM121 expression in NSCLC tissues was significantly higher than that in para-carcinoma tissues, both at the mRNA and protein level. The POM121 expression was related to sex, advanced differentiation, tumor diameter, lymph node metastases, distant metastases, American Joint Committee on Cancer (AJCC) stage, venous invasion, and perineural invasion in NSCLC. Kaplan-Meier analysis indicated that NSCLC patients with high POM121 expression had poor overall survival. Downregulation of POM121 inhibited cell proliferation, clone formation, migration and invasion. TGF-β/SMAD and PI3K/AKT pathways were involved in POM121-induced functional changes in NSCLC cells. CONCLUSION: POM121 plays an oncogenic role in NSCLC through TGF-β/SMAD and PI3K/AKT pathways. POM121 expression is a potential independent prognostic factor for NSCLC.

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Association between survivin gene promoter -31G/C and -644C/T polymorphisms and non-small cell lung cancer

Genetics and Molecular Research ◽

10.4238/2013.february.28.9 ◽

2013 ◽

Vol 12 (3) ◽

pp. 3975-3982 ◽

Cited By ~ 9

Author(s):

E. Aynaci ◽

E. Coskunpinar ◽

A. Eren ◽

O. Kum ◽

Y.M. Oltulu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Gene Promoter ◽

Small Cell ◽

Small Cell Lung ◽

Survivin Gene

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Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000495876 ◽

2018 ◽

Vol 51 (5) ◽

pp. 2324-2340 ◽

Cited By ~ 39

Author(s):

Xiuyuan Li ◽

Zenglei Zhang ◽

Hua Jiang ◽

Qiang Li ◽

Ruliang Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Promoter Region ◽

Small Cell ◽

Nsclc Cell ◽

Small Cell Lung ◽

Proliferation And Invasion

Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

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