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Genetic variant rs1058240 at the microRNA-binding site in the GATA3 gene may regulate its mRNA expression.

ABSTRACT: The GATA binding protein 3 (GATA3) is a member of a family of 6 GATA dual zinc finger transcription factors (GATA1-6), which are required for the development and morphogenesis of the mammary gland. GATA3 is considered to play a dual role in oncogenesis and cancer development, whereas somatic GATA3 mutations have been reported in breast cancer. Variants of the GATA3 genetic 3' untranslated region (3'UTR) microRNA (miRNA) binding sites have been associated with breast cancer risk. However, the roles of genetic variants in the GATA3 gene 3'UTR and its post-transcriptional regulation have not been fully elucidated. We discovered that rs1058240 in the GATA3 3'UTR displayed potential miRNA binding sites and this variant was found to be significantly associated with GATA3 mRNA expression (P=2.36E-07), suggesting that rs1058240 may be a putative variant mediating the post-transcriptional regulation of the GATA3 target gene. Further studies investigating the regulatory mechanism of GATA3 transcriptional activity are required to design novel strategies against breast cancer cell growth and differentiation.

SUBMITTER: Yang F

PROVIDER: S-EPMC3990192 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Genetic variant rs1058240 at the microRNA-binding site in the GATA3 gene may regulate its mRNA expression.

Yang Fang F Chen Fenxia F Gu Jun J Zhang Wenwen W Luo Jiayan J Guan Xiaoxiang X

Biomedical reports 20140314 3

The GATA binding protein 3 (GATA3) is a member of a family of 6 GATA dual zinc finger transcription factors (GATA1-6), which are required for the development and morphogenesis of the mammary gland. GATA3 is considered to play a dual role in oncogenesis and cancer development, whereas somatic <i>GATA3</i> mutations have been reported in breast cancer. Variants of the <i>GATA3</i> genetic 3' untranslated region (3'UTR) microRNA (miRNA) binding sites have been associated with breast cancer risk. Ho ...[more]

PMID: 24748983

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Project description:BackgroundMicroRNAs (miRNAs) are small noncoding RNAs that bind mRNA target transcripts and repress gene expression. They have been implicated in multiple diseases, such as cancer, but the mechanisms of this involvement are not well understood. Given the complexity and degree of interactions between miRNAs and target genes, understanding how miRNAs achieve their specificity is important to understanding miRNA function and identifying their role in disease.ResultsHere we report factors that influence miRNA regulation by considering the effects of both single and multiple miRNAs targeting human genes. In the case of single miRNA targeting, we developed a metric that integrates miRNA and mRNA expression data to calculate how changes in miRNA expression affect target mRNA expression. Using the metric, our global analysis shows that the repression of a given miRNA on a target mRNA is modulated by 3' untranslated region length, the number of target sites, and the distance between a pair of binding sites. Additionally, we show that some miRNAs preferentially repress transcripts with longer CTG repeats, suggesting a possible role for miRNAs in repeat expansion disorders such as myotonic dystrophy. We also examine the large class of genes targeted by multiple miRNAs and show that specific types of genes are progressively more enriched as the number of targeting miRNAs increases. Expression microarray data further show that these highly targeted genes are downregulated relative to genes targeted by few miRNAs, which suggests that highly targeted genes are tightly regulated and that their dysregulation may lead to disease. In support of this idea, cancer genes are strongly enriched among highly targeted genes.ConclusionOur data show that the rules governing miRNA targeting are complex, but that understanding the mechanisms that drive such control can uncover miRNAs' role in disease. Our study suggests that the number and arrangement of miRNA recognition sites can influence the degree and specificity of miRNA-mediated gene repression.

Dataset Information

Genetic variant rs1058240 at the microRNA-binding site in the GATA3 gene may regulate its mRNA expression.

Publications

Genetic variant rs1058240 at the microRNA-binding site in the GATA3 gene may regulate its mRNA expression.

Similar Datasets

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