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A polymorphism at the microRNA binding site in the 3' untranslated region of RYR3 is associated with outcome in hepatocellular carcinoma.

Peng C, Guo Z, Wu X, Zhang XL - Onco Targets Ther (2015)

Bottom Line: It was found that rs1044129 at the 3' UTR of RYR3 was related to postoperative survival in HCC, with the AA type associated with longer survival times as per the log-rank test.After adjusting with the Cox model, rs104419 was identified as an independent predictor of HCC survival (relative risk: 1.812; 95% confidence interval: 1.026-3.201; P=0.041).The SNP in the microRNA binding site of RYR3 can be used as a valuable biomarker when predicting HCC outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

ABSTRACT

Objective: MicroRNAs can bind to the 3' untranslated regions (UTRs) of messenger RNAs, where they interfere with the translation of targeting genes, thereby regulating cell differentiation, apoptosis, and tumorigenesis. In this study, three microRNA binding site single nucleotide polymorphisms (SNPs) located in the 3' UTR of RYR3 (rs1044129), C14orf101 (rs4901706), and KIAA0423 (rs1053667) were genotyped to assess their relationships with the risks and outcomes of hepatocellular carcinoma (HCC).

Methods: The SNPs were genotyped with the ligation detection reaction method. Renilla luciferase reporter assays were used to measure the binding affinity between microRNA 367 and RYR3. Survival curves were calculated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model.

Results: It was found that rs1044129 at the 3' UTR of RYR3 was related to postoperative survival in HCC, with the AA type associated with longer survival times as per the log-rank test. After adjusting with the Cox model, rs104419 was identified as an independent predictor of HCC survival (relative risk: 1.812; 95% confidence interval: 1.026-3.201; P=0.041). Luciferase analysis also indicated the different binding affinities between the SNPs of rs1044129 and microRNA 367.

Conclusion: The SNP in the microRNA binding site of RYR3 can be used as a valuable biomarker when predicting HCC outcomes.

No MeSH data available.


Related in: MedlinePlus

Renilla luciferase assay at 48 hours with modified psiCheck2 vector transfected in HeLa cell lines.Note: The Renilla luciferase activities are defined as the ratio of Renilla luciferase activities versus firefly luciferase activities.
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f2-ott-8-2075: Renilla luciferase assay at 48 hours with modified psiCheck2 vector transfected in HeLa cell lines.Note: The Renilla luciferase activities are defined as the ratio of Renilla luciferase activities versus firefly luciferase activities.

Mentions: To analyze the functional effect of rs1044129 on RYR3 expression, we constructed a vector containing the AA or GG genotype of rs1044129 in the 3′ UTR region of the Renilla luciferase gene and transfected them in HeLa cells. A dramatic reduction in Renilla luciferase activity was observed in the AA genotype (Figure 2). These results indicated that the rs1044129 SNP in the 3′ UTR of RYR3 changed its binding affinity with miRNAs, thus affecting its expression.


A polymorphism at the microRNA binding site in the 3' untranslated region of RYR3 is associated with outcome in hepatocellular carcinoma.

Peng C, Guo Z, Wu X, Zhang XL - Onco Targets Ther (2015)

Renilla luciferase assay at 48 hours with modified psiCheck2 vector transfected in HeLa cell lines.Note: The Renilla luciferase activities are defined as the ratio of Renilla luciferase activities versus firefly luciferase activities.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539090&req=5

f2-ott-8-2075: Renilla luciferase assay at 48 hours with modified psiCheck2 vector transfected in HeLa cell lines.Note: The Renilla luciferase activities are defined as the ratio of Renilla luciferase activities versus firefly luciferase activities.
Mentions: To analyze the functional effect of rs1044129 on RYR3 expression, we constructed a vector containing the AA or GG genotype of rs1044129 in the 3′ UTR region of the Renilla luciferase gene and transfected them in HeLa cells. A dramatic reduction in Renilla luciferase activity was observed in the AA genotype (Figure 2). These results indicated that the rs1044129 SNP in the 3′ UTR of RYR3 changed its binding affinity with miRNAs, thus affecting its expression.

Bottom Line: It was found that rs1044129 at the 3' UTR of RYR3 was related to postoperative survival in HCC, with the AA type associated with longer survival times as per the log-rank test.After adjusting with the Cox model, rs104419 was identified as an independent predictor of HCC survival (relative risk: 1.812; 95% confidence interval: 1.026-3.201; P=0.041).The SNP in the microRNA binding site of RYR3 can be used as a valuable biomarker when predicting HCC outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

ABSTRACT

Objective: MicroRNAs can bind to the 3' untranslated regions (UTRs) of messenger RNAs, where they interfere with the translation of targeting genes, thereby regulating cell differentiation, apoptosis, and tumorigenesis. In this study, three microRNA binding site single nucleotide polymorphisms (SNPs) located in the 3' UTR of RYR3 (rs1044129), C14orf101 (rs4901706), and KIAA0423 (rs1053667) were genotyped to assess their relationships with the risks and outcomes of hepatocellular carcinoma (HCC).

Methods: The SNPs were genotyped with the ligation detection reaction method. Renilla luciferase reporter assays were used to measure the binding affinity between microRNA 367 and RYR3. Survival curves were calculated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model.

Results: It was found that rs1044129 at the 3' UTR of RYR3 was related to postoperative survival in HCC, with the AA type associated with longer survival times as per the log-rank test. After adjusting with the Cox model, rs104419 was identified as an independent predictor of HCC survival (relative risk: 1.812; 95% confidence interval: 1.026-3.201; P=0.041). Luciferase analysis also indicated the different binding affinities between the SNPs of rs1044129 and microRNA 367.

Conclusion: The SNP in the microRNA binding site of RYR3 can be used as a valuable biomarker when predicting HCC outcomes.

No MeSH data available.


Related in: MedlinePlus