Differential methylation of TSP50 and mTSP50 genes in different types of human tissues and mouse spermatic cells

Huang, Yu; Wang, Yuezeng; Wang, Miao; Sun, Boqiao; Li, Yuxin; Bao, Yongli; Tian, Kegui; Xu, Haopeng

doi:10.1016/j.bbrc.2008.07.087

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…Previous studies have demonstrated that DNA methylation might regulate PRSS50 gene expression in different tissues and spermatic cells. 32 More interestingly, the gene was abnormally reactivated in many breast cancer biopsies, 33 and knockdown of PRSS50 induced cell apoptosis. 34 Understanding how increased promoter methylation and presumably decreased retinal expression of PRSS50 play a role in AMD pathogenesis will require further study.…”

Section: Discussionmentioning

confidence: 99%

“…32 Next, we limited the analysis to probes mapping near genes (using RefSeq coordinates for the genes and a 10 kb window for overlapping Illumina 450K probes) within regions previously associated with AMD in GWAS (1,408 probes within the 28 GWAS-positive regions), and utilized a Bonferroni-based correction to control for multiple testing (P < 0.05/1408).…”

Section: Discussionmentioning

confidence: 99%

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Differential DNA methylation identified in the blood and retina of AMD patients

Oliver¹,

Jaffe

Song

et al. 2015

Epigenetics

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Age-related macular degeneration (AMD) is a major cause of blindness in the western world. While genetic studies have linked both common and rare variants in genes involved in regulation of the complement system to increased risk of development of AMD, environmental factors, such as smoking and nutrition, can also significantly affect the risk of developing the disease and the rate of disease progression. Since epigenetics has been implicated in mediating, in part, the disease risk associated with some environmental factors, we investigated a possible epigenetic contribution to AMD. We performed genome-wide DNA methylation profiling of blood from AMD patients and controls. No differential methylation site reached genome-wide significance; however, when epigenetic changes in and around known GWASdefined AMD risk loci were explored, we found small but significant DNA methylation differences in the blood of neovascular AMD patients near age-related maculopathy susceptibility 2 (ARMS2), a top-ranked GWAS locus preferentially associated with neovascular AMD. The methylation level of one of the CpG sites significantly correlated with the genotype of the risk SNP rs10490924, suggesting a possible epigenetic mechanism of risk. Integrating genome-wide DNA methylation analysis of retina samples with and without AMD together with blood samples, we further identified a consistent, replicable change in DNA methylation in the promoter region of protease serine 50 (PRSS50). These methylation changes may identify sites in novel genes that are susceptible to non-genetic factors known to contribute to AMD development and progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential DNA methylation identified in the blood and retina of AMD patients

Oliver¹,

Jaffe

Song

et al. 2015

Epigenetics

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“…TSP50 is known as a CTA (47,59), is overexpressed in a high proportion of breast cancers (59), is a gene with promoter methylation associated with expression (22), and has a near-canonical CTCF target sequence in the promoter (data not shown). Further studies of this gene, its regulation, and its importance as a CTA may link it functionally to BORIS regulation of CTA and to BORIS as a CTA target for cancer treatment (36).…”

Section: Discussionmentioning

confidence: 99%

“…TSP50 is a testis-specific protease which is known to be a cancer testis antigen (47,59). The expression is regulated in part by methylation of the promoter (22), is negatively regulated by p53 (56), and is abnormally activated in a high proportion of breast cancers (59). The third gene, Gal3st1, which encodes CST, showed the greatest reduction in transcripts in BORIS Ϫ/Ϫ testis (Table 2).…”

Section: Targeted Disruption Of the Boris Genementioning

confidence: 99%

Expression of a Testis-Specific Form of Gal3st1 (CST), a Gene Essential for Spermatogenesis, Is Regulated by the CTCF Paralogous Gene BORIS

Suzuki

Kosaka-Suzuki

Pack

et al. 2010

Molecular and Cellular Biology

107

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Previously, it was shown that the CTCF paralogous gene, BORIS (brother of the regulator of imprinted sites) is expressed in male germ cells, but its function in spermatogenesis has not been defined. To develop an understanding of the functional activities of BORIS, we generated BORIS knockout (KO) mice. Mice homozygous for the null allele had a defect in spermatogenesis that resulted in small testes associated with increased cell death. The defect was evident as early as postnatal day 21 and was manifested by delayed production of haploid cells. By gene expression profiling, we found that transcript levels for Gal3st1 (also known as cerebroside sulfotransferase [CST]), known to play a crucial role in meiosis, were dramatically reduced in BORIS KO testes. We found that CST is expressed in testis as a novel testis-specific isoform, CST form F TS , that has a short exon 1f. We showed that BORIS bound to and activated the promoter of CST form F TS . Mutation of the BORIS binding site in the promoter reduced the ability of BORIS to activate the promoter. These findings define transcriptional regulation of CST expression as a critical role for BORIS in spermatogenesis.

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“…Previous studies have demonstrated that the TSP50 gene promoter's DNA methylation status most likely control the gene expression in different types of tissues [18]. DNA methylation is associated with TSP50 gene silencing in many normal tissues such as breast, lung and kidney.…”

Section: Introductionmentioning

confidence: 99%

High Expression of Testes-Specific Protease 50 Is Associated with Poor Prognosis in Colorectal Carcinoma

et al. 2011

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BackgroundTestes-specific protease 50 (TSP50) is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC) and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value.Methodology/Principal FindingsTSP50 mRNAs and proteins were detected in 7 CRC cell lines and 8 CRC specimens via RT-PCR and Western blot analysis. Immunohistochemical analysis of TSP50, p53 and carcinoembryonic antigen (CEA) with tissue microarrays composed of 95 CRCs, 20 colorectal adenomas and 20 normal colorectal tissues were carried out and correlated with clinicopathological characteristics and disease-specific survival for CRC patients. There was no significant correlation between the expression levels of TSP50 and p53 (P = 0.751) or CEA (P = 0.663). Abundant expression of TSP50 protein was found in CRCs (68.4%) while it was poorly expressed in colorectal adenomas and normal tissues (P<0.0001). Thus, CRCs can be distinguished from them with high specificity (92.5%) and positive predictive value (PPV, 95.6%). The survival of CRC patients with high TSP50 expression was significantly shorter than that of the patients with low TSP50 expression (P = 0.010), specifically in patients who had early-stage tumors (stage I and II; P = 0.004). Multivariate Cox regression analysis indicated that high TSP50 expression was a statistically significant independent risk factor (hazard ratio = 2.205, 95% CI = 1.214–4.004, P = 0.009).ConclusionOur data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors.

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Differential methylation of TSP50 and mTSP50 genes in different types of human tissues and mouse spermatic cells

Cited by 13 publications

References 17 publications

Differential DNA methylation identified in the blood and retina of AMD patients

Differential DNA methylation identified in the blood and retina of AMD patients

Expression of a Testis-Specific Form of Gal3st1 (CST), a Gene Essential for Spermatogenesis, Is Regulated by the CTCF Paralogous Gene BORIS

High Expression of Testes-Specific Protease 50 Is Associated with Poor Prognosis in Colorectal Carcinoma

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