Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma

Yanatatsaneejit, Pattamawadee; Chalermchai, Thep; Kerekhanjanarong, Virachai; Shotelersuk, Kanjana; Supiyaphun, Pakpoom; Mutirangura, Apiwat; Sriuranpong, Virote

doi:10.1016/j.oraloncology.2007.05.008

Cited by 44 publications

(34 citation statements)

References 19 publications

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“…[39][40] In fibroblasts, overexpression of Hrasls3 augments adipogenesis and accordingly Hrasls3 downregulation inhibits adipocyte differentiation. 34,[41][42] We find that, similar to the observations in adipogenesis, Hrasls3 expression increases during erythroid differentiation. We demonstrated that shRNA-mediated downregulation of Hrasls3 inhibits erythroid differentiation.…”

supporting

confidence: 85%

The DNA binding factor Hmg20b is a repressor of erythroid differentiation

Esteghamat

Dijk²,

Braun³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn erythroblasts, the CoREST repressor complex is recruited to target promoters by the transcription factor Gfi1b, leading to repression of genes mainly involved in erythroid differentiation. Hmg20b is a subunit of CoREST, but its role in erythropoiesis has not yet been established. Design and MethodsTo study the role of Hmg20b in erythropoiesis, we performed knockdown experiments in a differentiation-competent mouse fetal liver cell line, and in primary mouse fetal liver cells. The effects on globin gene expression were determined. We used microarrays to investigate global gene expression changes induced by Hmg20b knockdown. Functional analysis was carried out on Hrasls3, an Hmg20b target gene. ResultsWe show that Hmg20b depletion induces spontaneous differentiation. To identify the target genes of Hmg20b, microarray analysis was performed on Hmg20b knockdown cells and controls. In line with its association to the CoREST complex, we found that 85% (527 out of 620) of the deregulated genes are up-regulated when Hmg20b levels are reduced. Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation. Among the consistently up-regulated targets were embryonic β-like globins and the phospholipase HRASlike suppressor 3 (Hrasls3). We show that Hrasls3 expression is induced during erythroid differentiation and that knockdown of Hrasls3 inhibits terminal differentiation of proerythroblasts. ConclusionsWe conclude that Hmg20b acts as an inhibitor of erythroid differentiation, through the downregulation of genes involved in differentiation such as Hrasls3, and activation of repressors of differentiation such as Gfi1b. In addition, Hmg20b suppresses embryonic β-like globins.Key words: Hmg20b, CoREST, erythropoiesis, Gfi1b, Hrasls3, embryonic β-like globins.Citation: Esteghamat F, van Dijk TB, Braun H, Dekker S, van der Linden R, Hou J, Fanis P, Demmers J, van IJcken W, Özgür Z, Horos R, Pourfarzad F, von Lindern M, and

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supporting

confidence: 85%

The DNA binding factor Hmg20b is a repressor of erythroid differentiation

Esteghamat

Dijk²,

Braun³

et al. 2011

Haematologica

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“…The proposed mechanism of increased CCNA1 methylation is thought to be occurred in the interaction between E6/E7 and DNA methyltransferase on the CCNA1 promoter, leading to promote methylation and gene silencing. To this end, the function of cyclin A1 is likely to be as a tumor suppressor and involvement in the DNA repair mechanism (Muller-Tidow et al, 2004;Tokumaru et al, 2004;Kitkumthorn et al, 2006;Yanatatsaneejit et al, 2008). Consequently, in contrast to HPV infection involved in the early stage cervical cancer, cyclin A1 could likely lose DNA repair function, which may be crucial in the development of high-grade epithelial lesions.…”

Section: Discussionmentioning

confidence: 99%

CCNA1 Promoter Methylation: a Potential Marker for Grading Papanicolaou Smear Cervical Squamous Intraepithelial Lesions

Chujan

Kitkumthorn²,

Siriangkul³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease. Objectives: The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio. Methods: In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), lowgrade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR. Results: The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters. Conclusion: CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+using cervical cytology samples.

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“…16 Methylation of this gene is associated with nasopharyngeal carcinoma. 17 Several nonsynonymous SNPs in exons 12, 14 and 17 of LOH11CR2A have been detected in breast, lung and ovarian cancer patients. 16,18 PTT analysis revealed 9% mutation of this gene in breast cancer.…”

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confidence: 99%

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

Mazumder

Mitra

Singh

et al. 2011

Intl Journal of Cancer

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To understand the importance of frequent deletion of chromosomal 11q23.3-24.3 region in cervical carcinogenesis, alterations (deletion/methylation/mutation/expression) of the candidate genes LOH11CR2A, EI24 and CHEK1 located in the region were analyzed in 29 cervical intraepithelial neoplasia (CIN), 112 cervical carcinoma (CACX) samples and two CACX cell lines. The deletion frequency of these genes was low in CIN than in CACX [CIN: CHEK1: 28%, EI24: 21%, LOH11CR2A: 15% and CACX: CHEK1: 51%, EI24: 41%, LOH11CR2A: 36%]. Similar trend was seen in promoter methylation of these genes [CIN: CHEK1: 10%, EI24: 3%, LOH11CR2A: 3% and CACX: CHEK1: 55%, EI24: 31%, LOH11CR2A: 14%]. Mutations of the genes are a rare event. Overall alterations (deletion and methylation) of CHEK1 and EI24 were associated with progression of CACX. Quantitative mRNA expression analysis showed reduced expression of the three genes in concordance to their molecular alterations. A shorter isoform of CHEK1 lacking exon 8, hence impaired in substrate binding capacity, was found in two samples. Immunohistochemical analysis showed nuclear expression of Chek1, p-Chek1 and Ei24 in tumor tissues, whereas the cell lines exhibited both nuclear and cytoplasmic expression of Chek1 and Ei24, as is also evident from Western blot analysis suggesting differential localization of the proteins. Alterations of CHEK1 and EI24 coupled with tumor stage and early sexual debut ( 19 years) predicted worst prognosis. Thus, our data suggest that inactivation of EI24 and CHEK1 through two independent mechanisms contributes to the development of CACX.Worldwide, cervical cancer (CACX) is one of the most deadly cancers among women and occupies second position among females in eastern India (Kolkata). 1 Infection by highrisk human papillomavirus (HPV) is a major cause of CACX 2 along with other etiological factors, such as use of oral contraceptives, precocious marriage, multiparity and smoking. 1,3 As HPV infections in most cases do not lead to cancer, and even a long latency period for the cancerous outcome in infected women suggests involvement of additional genetic alterations like functional inactivation of tumor suppressor genes (TSGs) or activation of oncogenes. 4 Investigations showing frequent chromosomal deletion in 11q23-q24 (20.4 Mb) in cervix, 5-7 breast, 8,9 lung, 10 colon 11 and ovarian 12 cancer and functional chromosome-transfer

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Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma

Cited by 44 publications

References 19 publications

The DNA binding factor Hmg20b is a repressor of erythroid differentiation

The DNA binding factor Hmg20b is a repressor of erythroid differentiation

CCNA1 Promoter Methylation: a Potential Marker for Grading Papanicolaou Smear Cervical Squamous Intraepithelial Lesions

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

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