High-resolution melting (HRM) analysis for the detection of single nucleotide polymorphisms in microRNA target sites

Lin, Pei‐Chin; Liu, Ta-Chih; Chang, Chun‐Chi; Chen, Yung-Hsiu; Chang, Jan-Gowth

doi:10.1016/j.cca.2012.03.007

Cited by 9 publications

(7 citation statements)

References 43 publications

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“…They further showed that this SNP created an illegitimate binding site for miR-337-5p, which reduced levels of NPM1 mRNA and protein. MiRSNPs in PLA2G2A, IL-16 and NOD2 were also studied in acute leukemia but no significant differences in the genotype frequencies between leukemia patients and control group were detected [23]. …”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid leukemias and affect microRNA binding

Dzikiewicz‐Krawczyk

Macieja

Mały³

et al. 2014

J Hematol Oncol

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BackgroundMicroRNA dysregulation is a common event in leukemia. Polymorphisms in microRNA-binding sites (miRSNPs) in target genes may alter the strength of microRNA interaction with target transcripts thereby affecting protein levels. In this study we aimed at identifying miRSNPs associated with leukemia risk and assessing impact of these miRSNPs on miRNA binding to target transcripts.MethodsWe analyzed with specialized algorithms the 3′ untranslated regions of 137 leukemia-associated genes and identified 111 putative miRSNPs, of which 10 were chosen for further investigation. We genotyped patients with acute myeloid leukemia (AML, n = 87), chronic myeloid leukemia (CML, n = 140), childhood acute lymphoblastic leukemia (ALL, n = 101) and healthy controls (n = 471). Association between SNPs and leukemia risk was calculated by estimating odds ratios in the multivariate logistic regression analysis. For miRSNPs that were associated with leukemia risk we performed luciferase reporter assays to examine whether they influence miRNA binding.ResultsHere we show that variant alleles of TLX1_rs2742038 and ETV6_rs1573613 were associated with increased risk of childhood ALL (OR (95% CI) = 3.97 (1.43-11.02) and 1.9 (1.16-3.11), respectively), while PML_rs9479 was associated with decreased ALL risk (OR = 0.55 (0.36-0.86). In adult myeloid leukemias we found significant associations between the variant allele of PML_rs9479 and decreased AML risk (OR = 0.61 (0.38-0.97), and between variant alleles of IRF8_ rs10514611 and ARHGAP26_rs187729 and increased CML risk (OR = 2.4 (1.12-5.15) and 1.63 (1.07-2.47), respectively). Moreover, we observed a significant trend for an increasing ALL and CML risk with the growing number of risk genotypes with OR = 13.91 (4.38-44.11) for carriers of ≥3 risk genotypes in ALL and OR = 4.9 (1.27-18.85) for carriers of 2 risk genotypes in CML. Luciferase reporter assays revealed that the C allele of ARHGAP26_rs187729 creates an illegitimate binding site for miR-18a-3p, while the A allele of PML_rs9479 enhances binding of miR-510-5p and the C allele of ETV6_rs1573613 weakens binding of miR-34c-5p and miR-449b-5p.ConclusionsOur study implicates that microRNA-binding site polymorphisms modulate leukemia risk by interfering with the miRNA-mediated regulation. Our findings underscore the significance of variability in 3′ untranslated regions in leukemia.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid leukemias and affect microRNA binding

Dzikiewicz‐Krawczyk

Macieja

Mały³

et al. 2014

J Hematol Oncol

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“…A total of 15 publications regarding IL-16 gene polymorphisms and cancer risk were identified. Nine publications were excluded after reading the full article in detail, because they were editorial comment, letter, case report, other polymorphism of IL-16, without sufficient data, repeated literatures and violated HWE (Thomas et al, 2008;Obara et al, 2010;Azimzadeh et al, 2012;Batai et al, 2012;Lin et al, 2012;Deng et al, 2012;Du, et al, 2012;Hughes et al, 2013;Zhang et al, 2013). The study of Gao et al (2009b) presented separate OR by colorectal and gastric two cancer types and each of them was considered as a separate study.…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

Positive Association Between IL-16 rs11556218 T/G Polymorphism and Cancer Risk: a Meta-analysis

Peng²,

He³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…HRM does not require post-PCR separation, significant cost savings are achieved and becomes the most important mutation detection technique and has been widely applied in the polymorphisms detection and epigenetics studies [22, 37, 38]. HRM analysis was an efficient tool for studies of SNPs in miRNAs’ SNPs analysis in acute leukemia [39] and colorectal cancers [22] just two years ago. For evaluating the sensitivity and specificity of SNP scanning by HRM, Reed and Wittwer confirmed that the PCR products of 300 bp or less, all the heterozygous and wild-type cases were correctly called without error.…”

Section: Discussionmentioning

confidence: 99%

High-resolution melting analysis reveals genetic polymorphisms in MicroRNAs confer hepatocellular carcinoma risk in Chinese patients

Wang

Chen

et al. 2014

BMC Cancer

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BackgroundAlthough several single-nucleotide polymorphisms in microRNA (miRNA) genes have been associated with primary hepatocellular carcinoma, published findings regarding this relationship are inconsistent and inconclusive.MethodsThe high-resolution melting (HRM) analysis was used to determine whether the occurrence of the SNPs of miR-146a C > G (rs2910164), miR-196a2 C > T (rs11614913), miR-301b A > G (rs384262), and miR-499 C > T (rs3746444) differs in frequency-matched 314 HCC patients and 407 controls by age and sex.ResultsThe groups’ genotype distributions of miR-196a2 C > T and miR-499 C > T differed significantly (P < 0.01), both of them increased the risk of HCC in different dominant genetic models (P < 0.01); compared with individuals carrying one or neither of the unfavorable genotypes, individuals carrying both unfavorable genotypes (CT + CC) had a 3.11-fold higher HCC risk (95% confidence interval (CI), 1.89–5.09; P = 7.18 × 10−6). Moreover, the allele frequency of miR-499 C > T was significantly different between the two groups, and the HCC risk of carriers of the C allele was higher than that of carriers of the T allele (odds ratio, 1.53; 95% CI, 1.15-2.03; P = 0.003). Further, we found that the activated partial thromboplastin time (APTT) in HCC patients with miR-196a2 CC genotype was longer than patients with TT genotypes (P < 0.05), and HCC patients with miR-499 C allele had higher serum levels of direct bilirubin, globulin, γ-glutamyltranspeptidase, alkaline phosphatase, and lower serum cholinesterase (P < 0.05).ConclusionsOur findings suggest that the SNPs in miR-196a2 C > T and miR-499 C > T confer HCC risk and that affect the clinical laboratory characteristics of HCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-643) contains supplementary material, which is available to authorized users.

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High-resolution melting (HRM) analysis for the detection of single nucleotide polymorphisms in microRNA target sites

Cited by 9 publications

References 43 publications

Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid leukemias and affect microRNA binding

Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid leukemias and affect microRNA binding

Positive Association Between IL-16 rs11556218 T/G Polymorphism and Cancer Risk: a Meta-analysis

High-resolution melting analysis reveals genetic polymorphisms in MicroRNAs confer hepatocellular carcinoma risk in Chinese patients

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