A polymorphism at the miR-502 binding site in the 3′ untranslated region of the SET8 gene is associated with the risk of epithelial ovarian cancer

Wang, Cuiju; Guo, Zhanjun; Wu, Chensi; Li, Yan; Kang, Shan

doi:10.1016/j.cancergen.2012.04.010

Cited by 46 publications

(42 citation statements)

References 25 publications

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“…Epithelial ovarian cancer (EOC), which is categorized into serous, mucinous, endometrioid and non-clear cell types, accounts for 90% of all ovarian cancer (3,4). The earlier cancer is identified, the better the prognosis; however, ovarian cancer is difficult to detect early, as overt symptoms do not occur until later stages of the disease.…”

Section: Introductionmentioning

confidence: 99%

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Song

Zhao

et al. 2015

Oncology Letters

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Abstract. Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC). In addition, the biological significance of this polymorphism was investigated in the OVCAR3 ovarian cancer cell line. Risk association was evaluated in 479 cases of EOC patients and 431 controls. SNPs were analyzed by using polymerase chain reaction based restriction fragment length polymorphism assay. miR-196a expression was evaluated with reverse transcription polymerase chain reaction. The influence of miR-196a-2 rs11614913 T/C on EOC cell migration and invasion ability was further investigated in vitro. The results revealed significant differences in the homozygous CC genotype distribution in patients with EOC (n=479), compared with that of the control subjects (n=431; P=0.026). Analysis of the association between genotype and the risk of EOC revealed that individuals who carried the homozygous CC genotype were 1.34-fold more susceptible to EOC, compared with those carrying the wild-type TT and heterozygous CT genotypes [odds ratio, 1.34; 95% confidence interval, 1.04-2.17; P= 0.023].In addition, the role of this polymorphism in the production of mature miR-196a was investigated. Significantly enhanced production of mature miR-196a was revealed in the C-allelic compared with that of the T-allelic miR-196a-2 precursor (P<0.05). Further examination indicated that miR-196a significantly promoted cell migration and invasion ability in the human OVCAR3 ovarian cell line (P<0.05). In conclusion, the results indicated that the miR-196a-2 rs11614913 CC genotype may increase the risks of ovarian cancer by affecting the expression of mature miR-196a and enhancing cell migration/invasion. The current results provided evidence that the T>C polymorphism in the miR-196a-2 precursor may influence tumorigenesis and metastasis in EOC, and suggested that the functional SNP rs11614913 in the promoter region of pri-miR-196a-2 may be a potential indicator of EOC susceptibility in the population analyzed. IntroductionOvarian cancer only accounts for ~4% of cancer cases in women, but it is the eighth most common cause of cancerassociated mortality resulting from gynecological tumors worldwide (1,2). Epithelial ovarian cancer (EOC), which is categorized into serous, mucinous, endometrioid and non-clear cell types, accounts for 90% of all ovarian cancer (3,4). The earlier cancer ...

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Section: Introductionmentioning

confidence: 99%

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Song

Zhao

et al. 2015

Oncology Letters

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“…One of the 129 variants of the SET8 gene polymorphisms (rs16917496, TgC) is located within the miR-502-binding site in the 3'-UTR. In recent years, reports have showed that Shao-Di Yang et al the miR-502-binding site SNP in -the 3'-UTR of SET8 (rs16917496 C/T) was associated with the risk of breast cancer, hepatocellular carcinoma, epithelial ovarian cancer and so on (Song et al, 2009;Ding et al, 2012;Wang et al, 2012;Xu et al, 2013). However, there is no evidence showed a correlation between the miR-502-binding site SNP in the 3'-UTR of SET8 (rs16917496 C/T) and cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Association of a miR-502-Binding Site Single Nucleotide Polymorphism in the 3'-Untranslated Region of SET8 and the TP53 Codon 72 Polymorphism with Cervical Cancer in the Chinese Population

Yang¹,

Cai²,

Jiang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Objective: This study was conducted to identify whether polymorphic variants of set domain-containing protein 8 (SET8) and tumor protein p53 (TP53) codon 72, either independently or jointly, might be associated with increased risk for cervical cancer. Methods: We genotyped SET8 and TP53 codon 72 polymorphisms of peripheral blood DNA from 114 cervical cancer patients and 200 controls using the polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. Results: The frequency of SET8 CC (odds ratios (OR) = 2.717, 95% CI=1.436-5.141) or TP53 GG (OR=2.168, 95% CI=1.149-4.089) genotype was associated with an increased risk of cervical cancer on comparison with the SET8 TT or TP53 CC genotypes, respectively. In additional, interaction between the SET8 and TP53 polymorphisms increased the risk of cervical cancer in a synergistic manner, with the OR being 9.913 (95% CI=2.028-48.459) for subjects carrying both SET8 CC and TP53 GG genotypes. Conclusion: These data suggest that there are significant associations between the miR-502-binding site SNP in the 3'-UTR of SET8 and the TP53 codon 72 polymorphism with cervical cancer in Chinese, and there is a gene-gene interaction.

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“…SET8 has been shown to be correlated with a series of human tumors, such as hepatocellular cancer, breast cancer, ovarian cancer, and lung cancer (Song et al, 2009;Ding et al, 2012;Guo et al, 2012;Wang et al, 2012;Xu et al, 2013). However, no studies have demonstrated a correlation between SET8 and gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, targeting H4K20 for monomethylation (Fang et al, 2002;Nishioka et al, 2002) has been shown to have important functions in diverse biological processes, such as gene transcriptional control, replication origin modulation, genome integrity maintenance, cell cycle progression, and development (Abbas et al, 2010;Centore et al, 2010;Oda et al, 2010;Jørgensen et al, 2011;Li et al, 2011). Previous studies found that modulation of SET8 protein expression contributes to breast cancer and ovarian cancer susceptibility and affects the clinical outcome of hepatocellular carcinoma and non-small cell lung cancer (Song et al, 2009;Guo et al, 2012;Wang et al, 2012;Xu et al, 2013). Lower SET8 levels were found to be associated with longer survival in hepatic carcinoma and nonsmall cell lung cancer patients Xu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

SET8 expression is associated with overall survival in gastric cancer

Xl¹,

Zj²,

Xl³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. SET8, a member of the SET domain-containing methyltransferase, has been implicated in various biological processes. In this study, SET8 was immunostained in 100 samples of gastric cancer tissues and semi-quantified using the HSCORE method to determine the predictive value of SET8 expression levels for gastric cancer outcome. The relationship between SET8 expression and the 5-year survival rate of gastric cancer patients was assessed. High expression of SET8 was associated with a shorter survival time in gastric cancer patients, and the level of SET8 expression was found to be an independent predictor of gastric cancer outcome (relative risk = 1.939; 95% confidence interval = 1.025-3.668; P = 0.042). Analysis of SET8 levels may help in the identification of patient subgroups that are at high risk for poor disease outcomes.

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A polymorphism at the miR-502 binding site in the 3′ untranslated region of the SET8 gene is associated with the risk of epithelial ovarian cancer

Cited by 46 publications

References 25 publications

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Association of a miR-502-Binding Site Single Nucleotide Polymorphism in the 3'-Untranslated Region of SET8 and the TP53 Codon 72 Polymorphism with Cervical Cancer in the Chinese Population

SET8 expression is associated with overall survival in gastric cancer

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