Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer

Zheng, Hong; Song, Fengju; Zhang, Lína; Yang, Da; Ji, Ping; Wang, Yingmei; Almeida, Maria Inês; Calin, George A.; Hao, Xishan; Wei, Qingyi; Zhang, Wei; Chen, Kexin

doi:10.3892/ijo.2011.940

Cited by 25 publications

(28 citation statements)

References 38 publications

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“…Taken together, the results indicate that the derived T allele of rs1042538 can impair miR-124 IQGAP1 interaction in vivo and leads to an increased expression of IQGAP1 proteins in the brain. A previous report observed a similar effect of this SNP on IQGAP1 in breast samples [28].…”

Section: Resultssupporting

confidence: 69%

“…The observed higher tactual performance by those with the derived T allele provides a possible driving force if Darwinian positive selection has been acting on this SNP in East Asians. Interestingly, another report showed that the derived T allele of this SNP was also associated with a lower risk of developing breast cancer [28]. Aside from cognitive performance, there may then be other traits under selection.…”

Section: Discussionmentioning

confidence: 99%

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A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance

Yang

Zhang

et al. 2014

PLoS ONE

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As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a marked effect on cognitive performance. IQ motif containing GTPase activating protein 1 (IQGAP1), a scaffold protein, affects learning and memory in a dose-dependent manner. Its expression is regulated by miR-124 through the binding sites in the 3′UTR, where a SNP (rs1042538) exists in the core-binding motif. Here we showed that this SNP can influence the miR-target interaction both in vitro and in vivo. Individuals carrying the derived T alleles have higher IQGAP1 expression in the brain as compared to the ancestral A allele carriers. We observed a significant and male-specific association between rs1042538 and tactile performances in two independent cohorts. Males with the derived allele displayed higher tactual performances as compared to those with the ancestral allele. Furthermore, we found a highly diverged allele-frequency distribution of rs1042538 among world human populations, likely caused by natural selection and/or recent population expansion. These results suggest that current human populations still carry sequence variations that affect cognitive performances and that these genetic variants may likely have been subject to comparatively recent natural selection.

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Section: Resultssupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance

Yang

Zhang

et al. 2014

PLoS ONE

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“…We also reported that a miR-502 –binding site SNP in the 3′-UTR of the SET8 gene is associated with early age of breast cancer onset[46]. Recently, we found that genetic variants at the miR-124 –binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer[47].…”

Section: Principles Of Mirna Involvement In Human Cancersmentioning

confidence: 94%

Principles of microRNA involvement in human cancers

Ling

Zhang²,

Calin³

2011

Chin J Cancer

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Naturally occurring microRNAs (miRNAs), small non-coding RNAs of 19 to 24 nucleotides (nt), are encoded in the genomes of invertebrates, vertebrates, and plants. miRNAs act as regulators of gene expression during development and differentiation at the transcriptional, posttranscriptional, and/or translational levels, although most target genes are still elusive. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In this review, we present principles related to the basic and translational research that has emerged in the last decade, a period that can be truly considered the “miRNA revolution” in molecular oncology. These principles include the regulation mechanism of miRNA expression, functions of miRNAs in cancers, diagnostic values and therapeutic potentials of miRNAs. Furthermore, we present a compendium of information about the main miRNAs that have been identified in the last several years as playing important roles in cancers. Also, we orient the reader to several additional reviews that may provide a deeper understanding of this new and exciting field of research.

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“…We summarized in this review the SNPs within miRNA sequences, miRNA pathway genes, and miRNA binding sites that have been found to be significantly associated with cancer susceptibility[91],[97]–[112] (Table 1). Systematic analysis of the association between miRNA-related SNPs and cancer risk has been reported predominantly in two studies.…”

Section: Snps Among Mirnamentioning

confidence: 99%

Single-nucleotide polymorphisms among microRNA: big effects on cancer

Song

Chen²

2011

Chin J Cancer

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. Many miRNAs are found to play a significant role in cancer development either as tumor suppressor genes or as oncogenes. Examination of tumor-specific miRNA expression profiles in diverse cancers has revealed widespread deregulation of these molecules, whose loss and overexpression respectively have diagnostic and prognostic significance. Genetic variations, mostly single-nucleotide polymorphisms (SNPs) within miRNA sequences or their target sites, have been found to be associated with many kinds of cancers. In this review, we summarize the current knowledge of miRNAs including their biogenesis and role in cancer development, and finally, how SNPs among miRNAs affect miRNA biogenesis and contribute to cancer.

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Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer

Cited by 25 publications

References 38 publications

A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance

A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance

Principles of microRNA involvement in human cancers

Single-nucleotide polymorphisms among microRNA: big effects on cancer

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