Expression of Tumor Necrosis Factor Receptor-associated Factor 6 in Lung Cancer Tissues

Zhang, Xiu Ling; Dang, Yi; Li, Ping; Rong, Min; Hou, Xin Xi; Luo, Dian Zhong; Chen, Gang

doi:10.7314/apjcp.2014.15.24.10591

Cited by 17 publications

(18 citation statements)

References 30 publications

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“…Elevated TRAF6 expression has been detected in colon cancer ( 13 ), glioma ( 14 ), osteosarcoma ( 15 ), esophageal squamous cell carcinoma ( 16 ), breast cancer ( 17 ) and lung cancer tissues ( 18 , 19 ), and TRAF has been found to promote the proliferation of these cancer cells. In addition, inhibition of TRAF6 was reported to result in suppression of lung cancer cell proliferation and tumor formation ( 20 , 21 ), and the TRAF6 status was found to correlate inversely with response to chemotherapy in overall advanced non-small cell lung cancer patients ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

siRNA-induced TRAF6 knockdown promotes the apoptosis and inhibits the invasion of human lung cancer SPC-A1 cells

Huang

Lin

et al. 2016

Oncology Reports

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Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been found to be involved in multiple cancers. However, the effect of small interfering RNA (siRNA)-induced knockdown of TRAF6 on the biological behaviors of cancer cells remains unknown. Thus, the present study aimed to investigate the effect of siRNA-induced knockdown of TRAF6 on the biological behaviors of human lung cancer SPC-A1 cells. The expression of TRAF6 was determined in human lung adenocarcinoma A549, non-small cell lung cancer H1650, human airway epithelial Calu-3 and human lung cancer SPC-A1 cell lines using quantitative RT-PCR (qRT-PCR) and western blotting at the transcriptional and translational levels. TRAF6 expression was knocked down in the SPC-A1 cells using an siRNA technique, and the effects of TRAF6 knockdown on NF-κB activity, cell proliferation, apoptosis, cell cycle, invasion and migration of the SPC-A1 cells were determined using electrophoretic mobility shift assay (EMSA), cell proliferation assay, flow cytometry, Transwell invasion assay and scratch wound assay. In addition, the protein expression of CD24, CXCR4, MMP1, MMP2, MMP9, TWIST, TIMP-2 and Slug was quantified using western blotting assay. Western blotting and qRT-PCR assays showed upregulation of TRAF6 at both the translational and transcriptional levels in the Calu-3 and SPC-A1 cells, and K63-linked ubiquitination of TRAF6 and constitutive NF-κB activation were detected in the SPC-A1 cells. Knockdown of TRAF6 inhibited the migration and invasion and promoted the apoptosis of the SPC-A1 cells, but had little effect on cell proliferation and the cell cycle. In addition, siRNA-induced TRAF6 knockdown caused a marked reduction in the protein expression of CD24 and CXCR4, but had little effect on MMP-1, MMP-2, MMP-9, Twist, TIMP-2 or Slug expression. The present study demonstrated that TRAF6 is upregulated in human lung cancer cells, and siRNA-induced TRAF6 knockdown inhibits the invasion of lung cancer cells and promotes apoptosis. It is suggested that TRAF6 may be a promising target for the therapy of lung cancer.

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Section: Introductionmentioning

confidence: 99%

siRNA-induced TRAF6 knockdown promotes the apoptosis and inhibits the invasion of human lung cancer SPC-A1 cells

Huang

Lin

et al. 2016

Oncology Reports

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“…The intensity of the staining was scored as follows: 0 (negative); 1 (weak); 2 (moderate) and 3 (strong). The final pathological scores were calculated by multiplying the percentage and the staining intensity score as previously described [29, 30]. The positive staining results were confirmed when the scores were over two.…”

Section: Methodsmentioning

confidence: 99%

Clinical significance and effect of AEG-1 on the proliferation, invasion, and migration of NSCLC: a study based on immunohistochemistry, TCGA, bioinformatics, in vitro and in vivo verification

Zhang

Hou

et al. 2017

Oncotarget

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BackgroundAstrocyte elevated gene-1 (AEG-1) is related to the tumorigenesis and deterioration of different cancers, including non-small cell lung cancer (NSCLC). However, the effect of AEG-1 in NSCLC remains unclear. In this study, we aimed to investigate the clinical significance and effect of AEG-1 on biological function of NSCLC.ResultsAEG-1 was significantly overexpressed in NSCLC tissues and closely correlated to the deterioration of NSCLC based on tissue microarray, TCGA database and meta-analysis. After knock-down of AEG-1, the proliferation, migration and invasion of NSCLC cells were all inhibited, and the tumorigenic and angiogenic ability of NSCLC cells were weakened. Furthermore, the AEG-1 co-expressed genes were significantly related to AMPK signaling pathway based on bioinformatics approaches.Materials and MethodsA tissue microarray, the Cancer Genome Atlas (TCGA) database, as well as a meta-analysis were performed to analyze the relationship between AEG-1 and the clinicopathological parameters of NSCLC. Furthermore, immunocytochemistry, Western blot analysis, scratch assay, colony formation assay, Transwell migration and invasion assay and the chick embryo chorioallantoic membrane (CAM) model were conducted to explore the effect of AEG-1 on NSCLC in vitro and in vivo. Additionally, bioinformatics analyses were carried out to assess the potential pathways and networks of the co-expressed genes of AEG-1.ConclusionsAEG-1 is positively activated in the tumorigenesis and deterioration of NSCLC. We hypothesize that AEG-1 could play an important role in NSCLC via AMPK signaling pathway. Inhibiting the expression of AEG-1 is expected to become a novel method in the therapeutic strategies of NSCLC.

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“…Previous studies have linked one of the family members, TRAF6, to the oncogenesis, development and metastasis of numerous types of human cancer (23). Protein and mRNA overexpression of TRAF6 has been observed in human cancer tissues (24,25). In vitro, increased and consistent expression of TRAF6 has been identified in multiple human cancer cell lines (9).…”

Section: Discussionmentioning

confidence: 99%

Emodin suppresses angiogenesis and metastasis in anaplastic thyroid cancer by affecting TRAF6‑mediated pathways in�vivo and in�vitro

Shi

Zhou

2018

Mol Med Report

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Emodin has been recognized to be an anti-cancer agent against a number of types of human cancer. It was demonstrated that TNF receptor-associated factor 6 (TRAF6) was correlated with cancer angiogenesis and metastasis. The present study confirmed the association between TRAF6 and the angiogenesis/metastasis of anaplastic thyroid cancer (ATC). The anti-angiogenesis and metastatic effects of emodin, in addition to its molecular mechanisms in ATC, were investigated. A total of two ATC cell lines, namely 8505c and SW1736, were studied. ATC cells were implanted into nude mice to form xenografts or to establish lung metastasis models. Emodin was used to incubate ATC cells or to treat animals orally. An MTT assay was used to assess cell proliferation. A wound healing assay was employed to evaluate cell migration. ELISA analysis was used to detect the vascular endothelial growth factor (VEGF) content. Western blotting was used to determine the protein expression levels. In the in vivo study, cancer angiogenesis was assessed by micro vascular density measurement. The lung metastatic rate was the criterion for cancer metastasis. The results of the present study demonstrated that the proliferation of ATC was inhibited by emodin. The activation of the TRAF6/hypoxia inducible factor (HIF)-1α/VEGF and TRAF6/basigin (CD147)/matrix metalloproteinase-9 (MMP9) pathways were associated with the angiogenesis and metastasis of ATC. In a concentration-dependent manner, emodin inhibited the TRAF6/HIF-1α/VEGF and TRAF6/CD147/MMP9 signaling pathways to suppress angiogenesis and metastasis. In conclusion, emodin exerted anti-angiogenic and anti-metastatic activities in ATC by affecting TRAF6-mediated pathways.

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Expression of Tumor Necrosis Factor Receptor-associated Factor 6 in Lung Cancer Tissues

Cited by 17 publications

References 30 publications

siRNA-induced TRAF6 knockdown promotes the apoptosis and inhibits the invasion of human lung cancer SPC-A1 cells

siRNA-induced TRAF6 knockdown promotes the apoptosis and inhibits the invasion of human lung cancer SPC-A1 cells

Clinical significance and effect of AEG-1 on the proliferation, invasion, and migration of NSCLC: a study based on immunohistochemistry, TCGA, bioinformatics, in vitro and in vivo verification

Emodin suppresses angiogenesis and metastasis in anaplastic thyroid cancer by affecting TRAF6‑mediated pathways in�vivo and in�vitro

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