Silencing DNA methyltransferase 1 (DNMT1) inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK

Bai, Jian; Zhang, Xue; Hu, Kai; Liu, Bangqing; Li, Angui; Lin, Feng; Zhang, Lifei; Sun, Xin; Du, Zhenzong; Shi, Juan

doi:10.18632/oncotarget.9866

Cited by 38 publications

(26 citation statements)

References 33 publications

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“…The decreased expression of DAPK is associated with the methylation of gene promoter [ 8 , 9 ]. The methylation of DAPK promoter has been found to be an important epigenetic modification in several types of cancers [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis

et al. 2017

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BackgroundThe death-associated protein kinase (DAPK) is a tumor suppressor gene, which is a mediator of cell death of INF-γ–induced apoptosis. Aberrant methylation of DAPK promoter has been reported in patients with head and neck squamous cell carcinoma (HNSCC). However, the results of these studies are inconsistent. Hence, the present study aimed to evaluate the association between the promoter methylation of DAPK gene and HNSCC.MethodsRelevant studies were systematically searched in PubMed, Web of Science, Ovid, and Embase. The association between DAPK promoter methylation and HNSCC was assessed by odds ratio (ORs) and 95% confidence intervals (CI). To evaluate the potential sources of heterogeneity, we conducted the meta-regression analysis and subgroup analysis.ResultsEighteen studies were finally included in the meta-analysis. The frequency of DAPK promoter methylation in patients with HNSCC was 4.09-fold higher than the non-cancerous controls (OR = 3.96, 95%CI = 2.26–6.95). A significant association between DAPK promoter methylation and HNSCC was found among the Asian region and the Non-Asia region (Asian region, OR = 4.43, 95% CI = 2.29–8.58; Non-Asia region, OR = 3.39, 95% CI = 1.18–9.78). In the control source, the significant association between DAPK promoter methylation and HNSCC was seen among the autologous group and the heterogeneous group (autologous group, OR = 2.71, 95% CI = 1.49–4.93; heterogeneous group, OR = 9.50, 95% CI = 2.98–30.27). DAPK promoter methylation was significantly correlated with alcohol status (OR = 1.85, 95% CI = 1.07–3.21).ConclusionThe results of this meta-analysis suggested that aberrant methylation of DAPK promoter was associated with HNSCC.

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Section: Introductionmentioning

confidence: 99%

Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis

et al. 2017

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“…[ 15 , 16 ] Cell growth and proliferation in the human body are affected and controlled by numerous factors. [ 17 , 18 ] Notably, cell signaling proteins, growth factors and their receptors, apoptotic proteins and transcription factors, and the changes of these factors are closely associated with the occurrence and development of tumors. [ 19 ] TRIM proteins are a large family of proteins that have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation, and signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Correlation between tripartite motif-containing protein 44 protein expression and the prognosis of postoperative patients exhibiting skin squamous cell carcinoma

Guo

Cui

et al. 2018

Medicine

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Tripartite motif-containing protein 44 (TRIM44) plays an important role in the development and progression of some human cancers; however, its role in skin squamous cell carcinoma (SCC) remains unknown. The aim of the present study was to investigate TRIM44 expression and clinicopathological significance of TRIM44 in SCC.Immunohistochemistry (IHC) technique, reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate differences in TRIM44 protein expression in SCC and normal skin tissues.IHC showed that the positive rate of TRIM44 staining in SCC tissues 26.00% (9/30), while the positive rate of normal control group was 83.33% (25/30). The positive rate of TRIM44 staining in SCC tissues is significantly lower than normal skin tissue (P <.01). RT-PCR showed that the positive rates of TRIM44 mRNA expression in SCC tissues were 16.67% (5/30), but the positive rate of normal control group was 86.67% (26/30). TRIM44 mRNA expression in SCC group was significantly lower than that in the normal group (P <.01). Kaplan–Meier survival analysis showed that low expression was associated with poor overall survival in SCC patients (P =.004). Multi-factor survival analysis indicated that both low TRIM44 expression and tumor stage were independent factors affecting the overall survival of patients with SCC (P =.038 and P =.001, respectively). Low expression of TRIM44 in SCC was associated with staging (P =.009 and P =.008, respectively) and metastasis (P =.003 and P =.004, respectively).The levels of TRIM44 protein and TRIM44 mRNA in SCC are both lowly expressed which is strongly associated with tumor staging, metastasis, and poor survival. And it also is an independent factor affecting the overall survival of patients with SCC.

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“…CpG island methylation in the promoter region is a common epigenetic method of modifying gene expression. CpG methylation has been shown to modulate tumor progression in various cancer types, including esophageal squamous cell carcinoma (25,26), oral squamous cell carcinoma (27), salivary CXPA (28) and ACC (29). This modulation occurs mainly via the inactivation of tumor suppressor genes such as p16, MGMT, DAPK and RASSF1A.…”

Section: Discussionmentioning

confidence: 99%

Promoter hypermethylation may contribute to E‑cadherin repression in the human salivary carcinoma ex pleomorphic adenoma

Xia

et al. 2017

Int J Oncol

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The role of promoter methylation in the inactivation of E‑cadherin (CDH1) in salivary carcinoma ex pleomorphic adenoma (CXPA) is unknown. The objective of this study was to determine the role and potential clinical implications of CDH1 promoter methylation in salivary CXPA. The CDH1 promoter methylation status was determined by bisulfite sequencing PCR in 37 primary CXPA tissues and 2 CXPA cell lines. E‑cadherin expression levels were determined by immunohistochemical analysis of each tumor. E‑cadherin protein levels and CDH1 mRNA levels were examined by immunoblotting and quantitative real-time PCR, respectively, in 2 CXPA cell lines. Cells were treated with 5‑Aza-dC or TGF‑β1 to test the influence of promoter methylation on CDH1 mRNA and protein expression. Associations between CDH1 molecular alterations and patients' clinicopathologic characteristics and prognosis were statistically evaluated. CDH1 promoter hypermethylation was detected in 21 of 37 tumors (56.76%). Of these 37 tumors, 13 tumors (35.14%) showed low E‑cadherin expression. Tumors that had CDH1 promoter methylation had a histological tendency toward luminal differentiation (P=0.004), high tumor grade (P=0.005), high T stage (P=0.024) and high TNM stage (P=0.038) compared with tumors that did not. The two CXPA cell lines exhibited an inverse relationship between CDH1 promoter methylation status and CDH1 mRNA and protein expression. Treatment of the hypermethylated cell line with 5‑Aza-dC restored CDH1 mRNA and E‑cadherin protein expression. The induction of hypermethylation by TGF‑β1 resulted in the repression of CDH1 mRNA and protein expression. CDH1 is commonly silenced in CXPA through promoter methylation. CDH1 methylation is closely related to tumor cell differentiation, histological grade, lymph node metastasis and advanced TNM stage, indicating that CDH1 methylation may play a role in the initiation and progression of CXPA.

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Silencing DNA methyltransferase 1 (DNMT1) inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK

Cited by 38 publications

References 33 publications

Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis

Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis

Correlation between tripartite motif-containing protein 44 protein expression and the prognosis of postoperative patients exhibiting skin squamous cell carcinoma

Promoter hypermethylation may contribute to E‑cadherin repression in the human salivary carcinoma ex pleomorphic adenoma

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