Characterization of the Promoter of the Murine mac25 Gene

Kanemitsu, Noriyuki; Kato, Mitsuo; Miki, Tsuneharu; Komatsu, Sei; Okazaki, Yasushi; Hayashizaki, Yoshihide; Sakai, Toshiyuki

doi:10.1006/bbrc.2000.3944

Cited by 9 publications

(6 citation statements)

References 23 publications

(27 reference statements)

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“…As previously reported, overexpression of IGFBP7 can promote apoptosis in cancers of the prostate (26), colorectum (27), thyroid (28), and breast (29). IGFBP7 could be silenced by promoter hyper-methylation in multiple neoplastic tissues (37)(38)(39). In this study, we report that ADAR2-mediated editing can protect IGFBP7 from cleavage in vitro and in vivo, and the integrity is essential for IGFBP7 to induce apoptosis in ESCCs.…”

Section: Discussionsupporting

confidence: 70%

ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma

Chen

Liao

Zhang

et al. 2016

International Journal of Oncology

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Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is characterized by heterogeneous genetic and epigenetic changes. Recently, A-to-I RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), was found to be aberrantly regulated during tumorigenesis. We previously reported that ADAR2 was downregulated in ESCC but its role was unclear. Thus, we report here that overexpression of ADAR2 can induce apoptosis in ESCC cell lines and inhibit tumor growth in vitro and in vivo. ADAR2 knockdown inhibited apoptosis in ADAR2 highly expressing tumor cells. RNA-seq assay showed that ADAR2, not ADAR1 or active-site-mutated ADAR2, could edit insulin-like growth factor binding protein 7 (IGFBP7) mRNA in ESCC. IGFBP7 knockdown or ADAR2 catalytic activity destruction abolished the pro-apoptotic function of ADAR2. Mechanistically, RNA editing may stabilize IGFBP7 protein by changing the protease recognition site of matriptase and this is essential for IGFBP7 to induce apoptosis. Western blotting revealed that ADAR2 overexpression could induce IGFBP7-dependent inhibition of Akt signaling. Thus, our data indicate that ADAR2 suppresses tumor growth and induces apoptosis by editing and stabilizing IGFBP7 in ESCC, and this may represent a novel therapeutic target for treating ESCC.

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Section: Discussionsupporting

confidence: 70%

ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma

Chen

Liao

Zhang

et al. 2016

International Journal of Oncology

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“…A large body of evidence suggests that IGFBP7 functions as an oncosuppressor gene in human prostate, breast, lung and colorectal cancer, as it regulates cell proliferation, cell adhesion, cellular senescence and angiogenesis (Akaogi et al, 1996;Sprenger et al, 1999;Wilson et al, 2002;Burger et al, 2005;Ruan et al, 2006;Chen et al, 2007;Sato et al, 2007). IGFBP7 is silenced by promoter hypermethylation in several neoplastic tissues, including colorectal and gastric cancers (Kanemitsu et al, 2000;Ahmed et al, 2003;Lin et al, 2007). More recently, IGFBP7 has been shown to mediate senescence in melanocytes, and to suppress melanoma growth in vivo by inducing apoptosis (Wajapeyee et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

IGFBP7: an oncosuppressor gene in thyroid carcinogenesis

et al. 2010

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Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein involved in several cellular processes, including proliferation, senescence and apoptosis. Loss of IGFBP7 expression is a critical step in the development of human tumors, including melanoma and colon cancer. By microarray gene expression studies, we have detected downregulation of IGFBP7 gene expression in follicular and papillary thyroid tumors in comparison with normal thyroid tissue. Evaluation of publicly available PTC microarray gene expression data sets confirmed, in a consistent fraction of tumors, the downregulation of IGFBP7 transcript levels. The functional consequence of IGFBP7 downregulation was addressed in the PTCderived NIM1 cell line in which IGFBP7 expression is repressed by promoter hypermethylation. Exposure to soluble IGFBP7 protein or restoration of IGFBP7 expression by complementary DNA transfection reduced growth rate, migration, anchorage-independent growth and tumorigenicity of NIM1 cells. We show that the effects of IGFBP7 are related to apoptosis. Our data suggest that loss of IGFBP7 expression has a functional role in thyroid carcinogenesis, and it may represent a possible basis for therapeutic strategies.

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“…In an early study for the characterization of the murine mac25 gene promoter, Sp1 and methylation were found to regulate the expression of IGFBP7 [36]. More recently, the transcriptional factor AP-1 was identified to be able to bind to the promoter region of IGFBP7 , participating in regulation of the IGFBP7 expression by BRAF600E in melanoma cells [33].…”

Section: Discussionmentioning

confidence: 99%

The functional IGFBP7 promoter −418G>A polymorphism and risk of head and neck cancer

Huang

Niu

Liu

et al. 2010

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Insulin-like growth factor binding protein 7 (IGFBP7) functions mostly independent of the IGF signaling pathway and acts as a tumor suppressor in multiple cancers, but roles of IGFBP7 genetic variants in cancer remains unknown. In a hospital-based study of 1,065 patients with squamous cell carcinoma of head and neck (SCCHN) and 1,112 cancer-free controls of non-Hispanic whites, we investigated associations between two putatively functional IGFBP7 promoter single nucleotide polymorphisms (SNPs) (−702G>C, rs11573014 and −418G>A, rs4075349) and SCCHN risk. A significantly lower SCCHN risk was observed in those subjects carrying −418AG (adjusted OR=0.82, 95% CI=0.67–0.99) and −418AG+AA (adjusted OR=0.82, 95% CI=0.69–0.99) genotypes than those carrying the −418GG genotype, but not for the −702G>C SNP. However, those subjects carrying two common homozygous genotypes of these two SNPs (−418GG and −702GG) had an increased risk (adjusted OR=1.21, 95% CI=1.00-0.1.46) than did those carrying variant genotypes (−418AG+AA and −702CG+CC). This increased risk was more evident in subgroups of never smokers and subjects with oral cancer. Further functional analysis showed that the IGFBP7 −418A allele had significantly higher promoter and DNA-protein binding activities than did the G allele, suggesting a tumor suppressor role of this allelic change in the SCCHN etiology. We conclude that the functional variant −418 G>C in the IGFBP7 promoter is associated with reduced risk of SCCHN, likely by enhancing the IGFBP7 promoter and DNA-protein binding activities. Larger studies are needed to validate our findings.

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Characterization of the Promoter of the Murine mac25 Gene

Cited by 9 publications

References 23 publications

ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma

ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma

IGFBP7: an oncosuppressor gene in thyroid carcinogenesis

The functional IGFBP7 promoter −418G>A polymorphism and risk of head and neck cancer

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