A MicroRNA-7 Binding Site Polymorphism in HOXB5 Leads to Differential Gene Expression in Bladder Cancer

Luo, Junpeng; Cai, Qingqing; Wang, Wei; Huang, Hui; Zeng, Hong; Wang, He; Deng, Weixi; Yu, Hao; Chan, Eddie Shu‐Yin; Ng, Chi‐Fai; Huang, Jian; Lin, Tianxin

doi:10.1371/journal.pone.0040127

Cited by 43 publications

(39 citation statements)

References 28 publications

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“…Luo et al 57 identified the first prognostic miRNA binding SNP for bladder cancer in the 3'-UTR of the HOXB5 gene associated with risk of high grade and high stage bladder cancer. HOXB5 is over-expressed in bladder cancer tissues and promotes cell proliferation and migration in bladder cancer cells.…”

Section: Snps In Mirna Binding Sites As Prognostic Biomarkersmentioning

confidence: 99%

SNPs in MicroRNA Binding Sites as Prognostic and Predictive Cancer Biomarkers

Preskill

Weidhaas

2013

Crit Rev Oncog

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Single nucleotide polymorphisms within microRNA (miRNA) binding sites comprise a novel genre of cancer biomarkers. Since miRNA regulation is dependent on sequence complementarity between the mRNA transcript and the miRNA, even single nucleotide aberrations can have significant effects. Over the past few years, many examples of these functional miRNA binding site SNPs have been identified as cancer biomarkers. While most of the research to date focuses on associations with cancer risk, more and more studies are linking these SNPs to cancer prognosis and response to treatment as well. This review summarizes the state of the field and draws importance to this rapidly expanding area of cancer biomarkers.

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Section: Snps In Mirna Binding Sites As Prognostic Biomarkersmentioning

confidence: 99%

SNPs in MicroRNA Binding Sites as Prognostic and Predictive Cancer Biomarkers

Preskill

Weidhaas

2013

Crit Rev Oncog

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“…In particular, miRNAs require almost perfect complementarity at the seed sites to bind and to reduce the protein levels of targets [48]. However, studies have shown that SNPs in the no-seed sequence of miRNA may also affect miRNA-binding ability [49][50][51]. Our results suggested that the bovine TNP1 gene is a target of bta-miR-204 and btamiR-532.…”

Section: Discussionmentioning

confidence: 69%

TNP1 Functional SNPs in bta-miR-532 and bta-miR-204 Target Sites Are Associated with Semen Quality Traits in Chinese Holstein Bulls1

Zhang

Yang

et al. 2015

Biology of Reproduction

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Transition nuclear proteins (TNPs), major proteins found in the chromatin of condensing spermatids, have been implicated in spermatogenesis and male fertility. In this study, DNA samples were collected from 404 Chinese Holstein bulls and sequenced to identify genetic variants in the 3'-untranslated region (UTR) of TNP1 and to investigate genetic variations in the TNP1 gene and their common haplotypes. This study was also conducted to determine whether these variations affect bovine semen quality traits and expression levels by PCR-restriction fragment length polymorphism, bioinformatics analyses, quantitative real-time PCR (qPCR), and fluorescence assay. Results showed that one new single-nucleotide polymorphism (SNP; g. 528 G>A, ss1388116558) and one reported SNP (g. 442 A>G, rs110469441) were found in the 3'-UTR of the TNP1 gene. Bioinformatics analysis results revealed that both loci were located in bta-miR-532-binding and bta-miR-204-binding regions, respectively. Association studies revealed that bulls with H1H1 (AGAG) and H1H3 (AGGG) haplotype combinations exhibited a lower deformity rate than those with other haplotype combinations (P < 0.05). The qPCR results showed that the relative mRNA expression of TNP1 in bulls with H1H1 haplotype combination was significantly higher than that in bulls with H4H4 haplotype combination (P < 0.05). MicroRNA qPCR results suggested that bta-miR-532 expression was downregulated by 5-fold in adult bull testicular tissues compared with that in fetal bull testicular tissues; by contrast, bta-miR-204 expression was downregulated by 1.6-fold. Luciferase assay results also indicated that TNP1 expression was directly targeted by bta-miR-532 and bta-miR-204 in murine Leydig tumor cell lines. These results provide the first indication of g. 442 A>G-mediated and g. 528 G>A-mediated translational suppression in which SNPs altered the binding of bta-miR-204 and bta-miR-532 to the 3'-UTR of TNP1; the mediated translational suppression could be involved in the regulation of TNP1 expression and may influence the morphological characteristics of Chinese Holstein bull sperm. We propose that SNPs on the TNP1 3'-UTR may help select semen quality trait in Chinese Holstein bulls in the dairy industry.

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“…58 A number of studies have shown that SNPs in miRNA binding sites are associated with diseases 32,59,60 and may significantly alter miRNA binding to associated gene transcripts. 61,62 In particular, 8 SNPs in the NOD2 gene were recently analyzed for associations with atopic phenotypes in a large German adult population (n = 1875). 36 Of particular interest in this report is that an SNP with an A allele at rs3135500 (G4384A) is located in the NOD2 putative miRNA binding site for miR-192.…”

Section: Discussionmentioning

confidence: 99%

NOD2 Expression is Regulated by microRNAs in Colonic Epithelial HCT116 Cells

Chuang

Zhai

et al. 2014

Inflammatory Bowel Diseases

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Background Crohn's disease (CD) is associated with defective sensing of pathogens in genetically susceptible individuals. Nucleotide-binding oligomerization domain containing 2 (NOD2) mutations in coding regions are strongly linked to CD pathogenesis. Our laboratory has reported that microRNAs (miRNAs) are differentially expressed in CD. However, miRNA regulation of NOD2 remains unknown. This study was designed to determine whether miRNAs regulate NOD2 expression as well as downstream nuclear factor kappaB activation and inflammatory responses in colonic epithelial HCT116 cells. Methods NOD2 and miRNA expression in stimulated HCT116 cells were assessed by quantitative reverse transcription–polymerase chain reaction. Regulation of NOD2 expression by miRNAs was determined by luciferase reporter construct assays and transfection of specific miRNA mimics. Regulation of NOD2 signaling and immune response by miRNAs was assessed by transfection of mimics followed by muramyl dipeptide stimulation. Results Muramyl dipeptide-induced increases in NOD2, interleukin-8, and CXCL3 expression were inversely associated with miRNA expression. Overexpression of miR-192, miR-495, miR-512, and miR-671 suppressed NOD2 expression, muramyl dipeptide-mediated NF-κB activation, and messenger RNA expressions of interleukin-8 and CXCL3 in HCT116 cells. A single-nucleotide polymorphism (rs3135500) located in the NOD2 3′-untranslated region significantly reduced miR-192 effects on NOD2 gene expression. Conclusions To our knowledge, this is the first report demonstrating that miRNAs regulate NOD2 and its signaling pathway. Four miRNAs downregulate NOD2 expression, suppress NF-κB activity, and inhibit interleukin-8 and CXCL3 messenger RNA expression. Treatment of CD with miRNAs may represent a potential anti-inflammatory therapeutic strategy in CD patients with and without NOD2 gene mutations.

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A MicroRNA-7 Binding Site Polymorphism in HOXB5 Leads to Differential Gene Expression in Bladder Cancer

Cited by 43 publications

References 28 publications

SNPs in MicroRNA Binding Sites as Prognostic and Predictive Cancer Biomarkers

SNPs in MicroRNA Binding Sites as Prognostic and Predictive Cancer Biomarkers

TNP1 Functional SNPs in bta-miR-532 and bta-miR-204 Target Sites Are Associated with Semen Quality Traits in Chinese Holstein Bulls1

NOD2 Expression is Regulated by microRNAs in Colonic Epithelial HCT116 Cells

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