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Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin D1 splicing variant expression in Chinese population.

Zeng Z, Tu J, Cheng J, Yao M, Wu Y, Huang X, Xie X, Zhang X, Lu F, Chen X - Tumour Biol. (2015)

Bottom Line: The expression of both cyclins D1a and D1b decreased in HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues as compared with normal liver tissues (p = 0.045, p = 0.034).Collectively, our data suggest that G870A polymorphism has only very limited predictive value for HBV-related HCC.Both cyclins D1a and D1b could promote cell proliferation, which might contribute to the potential oncogenic role of cyclin D1 variants during the precancerous cirrhotic stage of hepatocarcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

ABSTRACT
The G870A polymorphism in the exon 4/intron 4 boundary of CCND1 gene is thought to influence the generation of two mRNAs (cyclin D1a and cyclin D1b). The "A" allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. Herein, the tumor relevance of G870A polymorphism, the association between cyclin D1 variant expression and G870A genotype, and the oncogenic potential of cyclin D1 variants in HBV-related hepatocellular carcinoma (HCC) were examined. We found that there is no significant difference of G870A distribution among the HCC, chronic HBV (CHB) infection, cirrhotic CHB, and healthy control groups. Stratification analysis revealed that in younger patients (ages ≤ 50), cirrhotic CHB patients with AA genotype had an increased risk of developing HCC with odds ratio of 1.943 (95 % CI 1.022-3.694, p = 0.0411) as compared with AG/GG genotypes. The two variants were both transcripted from "A" and "G" alleles, and neither cyclin D1a nor D1b production was influenced by G870A genotype in HCC. The expression of both cyclins D1a and D1b decreased in HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues as compared with normal liver tissues (p = 0.045, p = 0.034). Overexpression of cyclin D1a or D1b could promote the cell proliferation and cell-cycle progression in Huh-7 and LO2 cell lines. Collectively, our data suggest that G870A polymorphism has only very limited predictive value for HBV-related HCC. Both cyclins D1a and D1b could promote cell proliferation, which might contribute to the potential oncogenic role of cyclin D1 variants during the precancerous cirrhotic stage of hepatocarcinogenesis.

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Relationship between cyclin D1a and cyclin D1b expression in HCC tissues. a The correlation of cyclin D1a and cyclin D1b expression level in 45 cases tumor tissues was analyzed by liner correction. b The correlation of cyclin D1a and cyclin D1b expression level in nontumor tissues was analyzed as in (a)
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Fig3: Relationship between cyclin D1a and cyclin D1b expression in HCC tissues. a The correlation of cyclin D1a and cyclin D1b expression level in 45 cases tumor tissues was analyzed by liner correction. b The correlation of cyclin D1a and cyclin D1b expression level in nontumor tissues was analyzed as in (a)

Mentions: As cyclins D1a and D1b are transcribed from the same gene, it is critical to determine whether the expression of cyclins D1a and D1b is coupled or independent factors in HCC. To address this question, we analyzed the correlation between cyclins D1a and D1b mRNA levels by using Pearson correlations analysis. As shown in Fig. 3a, the level of cyclin D1b had a significant linear correlation with cyclin D1a level in HCC tumor tissues (r = 0.7466, p < 0.0001). Likewise, the level of cyclin D1b also had a linear correlation with cyclin D1a level in the nontumor tissues (r = 0.33, p = 0.027), but it is weaker than that in HCC tumor tissues (Fig. 3b). These findings demonstrated that the expression of cyclin D1b might be determined in parallel on the same quantitative platform of cyclin D1a.Fig. 3


Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin D1 splicing variant expression in Chinese population.

Zeng Z, Tu J, Cheng J, Yao M, Wu Y, Huang X, Xie X, Zhang X, Lu F, Chen X - Tumour Biol. (2015)

Relationship between cyclin D1a and cyclin D1b expression in HCC tissues. a The correlation of cyclin D1a and cyclin D1b expression level in 45 cases tumor tissues was analyzed by liner correction. b The correlation of cyclin D1a and cyclin D1b expression level in nontumor tissues was analyzed as in (a)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4644212&req=5

Fig3: Relationship between cyclin D1a and cyclin D1b expression in HCC tissues. a The correlation of cyclin D1a and cyclin D1b expression level in 45 cases tumor tissues was analyzed by liner correction. b The correlation of cyclin D1a and cyclin D1b expression level in nontumor tissues was analyzed as in (a)
Mentions: As cyclins D1a and D1b are transcribed from the same gene, it is critical to determine whether the expression of cyclins D1a and D1b is coupled or independent factors in HCC. To address this question, we analyzed the correlation between cyclins D1a and D1b mRNA levels by using Pearson correlations analysis. As shown in Fig. 3a, the level of cyclin D1b had a significant linear correlation with cyclin D1a level in HCC tumor tissues (r = 0.7466, p < 0.0001). Likewise, the level of cyclin D1b also had a linear correlation with cyclin D1a level in the nontumor tissues (r = 0.33, p = 0.027), but it is weaker than that in HCC tumor tissues (Fig. 3b). These findings demonstrated that the expression of cyclin D1b might be determined in parallel on the same quantitative platform of cyclin D1a.Fig. 3

Bottom Line: The expression of both cyclins D1a and D1b decreased in HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues as compared with normal liver tissues (p = 0.045, p = 0.034).Collectively, our data suggest that G870A polymorphism has only very limited predictive value for HBV-related HCC.Both cyclins D1a and D1b could promote cell proliferation, which might contribute to the potential oncogenic role of cyclin D1 variants during the precancerous cirrhotic stage of hepatocarcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

ABSTRACT
The G870A polymorphism in the exon 4/intron 4 boundary of CCND1 gene is thought to influence the generation of two mRNAs (cyclin D1a and cyclin D1b). The "A" allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. Herein, the tumor relevance of G870A polymorphism, the association between cyclin D1 variant expression and G870A genotype, and the oncogenic potential of cyclin D1 variants in HBV-related hepatocellular carcinoma (HCC) were examined. We found that there is no significant difference of G870A distribution among the HCC, chronic HBV (CHB) infection, cirrhotic CHB, and healthy control groups. Stratification analysis revealed that in younger patients (ages ≤ 50), cirrhotic CHB patients with AA genotype had an increased risk of developing HCC with odds ratio of 1.943 (95 % CI 1.022-3.694, p = 0.0411) as compared with AG/GG genotypes. The two variants were both transcripted from "A" and "G" alleles, and neither cyclin D1a nor D1b production was influenced by G870A genotype in HCC. The expression of both cyclins D1a and D1b decreased in HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues as compared with normal liver tissues (p = 0.045, p = 0.034). Overexpression of cyclin D1a or D1b could promote the cell proliferation and cell-cycle progression in Huh-7 and LO2 cell lines. Collectively, our data suggest that G870A polymorphism has only very limited predictive value for HBV-related HCC. Both cyclins D1a and D1b could promote cell proliferation, which might contribute to the potential oncogenic role of cyclin D1 variants during the precancerous cirrhotic stage of hepatocarcinogenesis.

Show MeSH
Related in: MedlinePlus