Different expression pattern and significance of p14ARF-Mdm2-p53 pathway and Bmi-1 exist between gastric cardia and distal gastric adenocarcinoma

Yao, Dongying; Wang, Yuan; Xue, Liang; Wang, Heng-shu; Zhang, Jieying; Zhang, Xianghong

doi:10.1016/j.humpath.2012.08.009

Cited by 13 publications

(11 citation statements)

References 29 publications

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“…In contrast, some studies demonstrated that there was no obvious correlation between Bmi-1 and p16 INK4a (39). Yao et al (40) also reported no significant relationship among Bmi-1, p14 ARF and p53 in gastric adenocarcinoma. These conflicting data indicate that different mechanisms may be involved in the development of cancers.…”

Section: Discussionmentioning

confidence: 93%

Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44+ nasopharyngeal carcinoma cancer stem-like cells

Liu

et al. 2015

Oncology Reports

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Bmi-1 (B-cell-specific Moloney murine leukemia virus insertion site 1) is a member of the Polycomb group gene (PcG) family, which is involved in the proliferation, migration and tumorigenesis of several types of cancer stem cells (CSCs). However, its precise role and mechanism in CD44+ nasopharyngeal carcinoma (NPC) cancer stem-like cells (CSC-LCs) remain poorly understood. In our previous study, we successfully silenced Bmi-1 by short hairpin RNA (shRNA) in CD44+ NPC CSC-LCs and obtained stable Bmi-1 knockdown (KD) cell lines. In the present study, we tested the cell proliferation by CCK-8 assay and apoptosis by ﬂow cytometry. Scratch wound healing assay, together with Transwell migration and invasion assays were used to measure the migration and invasion capacity. We further evaluated the tumorigenicity of CD44+ NPC CSC-LCs transfected with Bmi-1 shRNA in vivo. Based on our results, knockdown of Bmi-1 by shRNA resulted in the inhibition of tumor proliferation, migration and invasion in vitro, followed by cell apoptosis. In addition, our results preliminarily demonstrated that inhibition of Bmi-1 expression by shRNA increased tumor apoptosis through the p16INK4a-p14ARF-p53 pathway. Bmi-1 silencing in CD44+ NPC CSC-LCs also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of Bmi-1 in the occurrence and development of NPC. Based on our findings, regulation of Bmi-1 in CD44+ NPC CSC-LCs may provide a potential molecular target for the therapy of NPC, and targeted silencing of Bmi-1 by shRNA may have clinical future implications in NPC therapy.

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Section: Discussionmentioning

confidence: 93%

Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44+ nasopharyngeal carcinoma cancer stem-like cells

Liu

et al. 2015

Oncology Reports

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“…In support of this proposal, Boroumand-Noughabi and colleagues 31 found a significantly higher serum level of soluble FasL in Iranian patients with GNCA versus those with GCA (p 5 0.005) suggesting difference in the efficacy of apoptosis in different gastric subtype tumors and/or patient immune reponse to the subtypes. Also, other data suggests that GCA is distinguished from GNCA by differences in risk factors, 32 tumor characteristics, 33 patterns of mRNA profiling and protein expression 34,35 and genetic alterations. 36 As well as being anatomically adjacent, GCA and esophageal squamous cell carcinoma (ESCC) occur at epidemic rates in this study population, share some etiological risk factors as well a GWAS risk variant in the PLCE1 gene.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in fas signaling pathway genes and risk of gastric cancer

Hyland

Lin

et al. 2013

Intl Journal of Cancer

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Populations in north central China are at high risk for gastric cancers (GC), and altered FAS-mediated cell signaling and/or apoptosis may contribute to this risk. We examined the association of 554 single nucleotide polymorphisms (SNPs) in 53 Fas signaling-related genes using a pathway-based approach in 1758 GC cases (1126 gastric cardia adenocarcinomas (GCA) and 632 gastric noncardia adenocarcinomas (GNCA)), and 2111 controls from a genome-wide association study (GWAS) of GC in ethnic Chinese. SNP associations with risk of overall GC, GCA and GNCA were evaluated using unconditional logistic regressions controlling for age, sex and study. Gene- and pathway-based associations were tested using the adaptive rank-truncated product (ARTP) method. Statistical significance was evaluated empirically by permutation. Significant pathway-based associations were observed for Fas signaling with risk of overall GC (P = 5.5E-04) and GCA (P = 6.3E-03), but not GNCA (P = 8.1E-02). Among examined genes in the Fas signaling pathway, MAP2K4, FAF1, MAPK8, CASP10, CASP8, CFLAR, MAP2K1, CAP8AP2, PAK2 and IKBKB were associated with risk of GC (nominal P < 0.05), and FAF1 and MAPK8 were significantly associated with risk of both GCA and GNCA (nominal P < 0.05). Our examination of genetic variation in the Fas signaling pathway is consistent with an association of altered Fas signaling and/or apoptosis with risk of GC. As one of the first attempts to investigate a pathway-level association, our results suggest that these genes and the Fas signaling pathway warrant further evaluation in relation to GC risk in other populations.

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“…20 These studies therefore indicate that p16, Rb, p14 ARF , and p53 gene activities are interconnected, and evolution has developed p14 ARF -p53 and p16 INK4a -Rb as complementary pathways for the control of human tumor development. 21 We have found differences in the p53 pathway between GCA and DGA; 22 however, whether there are different roles for the p16 INK4a -Rb pathway between two groups remains unclear.…”

Section: Introductionmentioning

confidence: 85%

“…20 We have demonstrated that expressions of p14 ARF -p53 pathway were significantly different between two entities. 22 Given different immunotypes of two pathways, it suggested that GCA might have some differences in cell proliferation and differentiation from DGA.…”

Section: Discussionmentioning

confidence: 99%

Different roles for p16^INK^4a‐Rb pathway and INK4a/ARF methylation between adenocarcinomas of gastric cardia and distal stomach

Xue

Ouyang

et al. 2014

J of Gastro and Hepatol

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Different expression pattern and significance of p14ARF-Mdm2-p53 pathway and Bmi-1 exist between gastric cardia and distal gastric adenocarcinoma

Cited by 13 publications

References 29 publications

Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44+ nasopharyngeal carcinoma cancer stem-like cells

Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44+ nasopharyngeal carcinoma cancer stem-like cells

Genetic variants in fas signaling pathway genes and risk of gastric cancer

Different roles for p16^INK^4a‐Rb pathway and INK4a/ARF methylation between adenocarcinomas of gastric cardia and distal stomach

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Different expression pattern and significance of p14ARF-Mdm2-p53 pathway and Bmi-1 exist between gastric cardia and distal gastric adenocarcinoma

Cited by 13 publications

References 29 publications

Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44+ nasopharyngeal carcinoma cancer stem-like cells

Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44+ nasopharyngeal carcinoma cancer stem-like cells

Genetic variants in fas signaling pathway genes and risk of gastric cancer

Different roles for p16INK4a‐Rb pathway and INK4a/ARF methylation between adenocarcinomas of gastric cardia and distal stomach

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Different roles for p16^INK^4a‐Rb pathway and INK4a/ARF methylation between adenocarcinomas of gastric cardia and distal stomach