Searching for potential microRNA-binding site mutations amongst known disease-associated 3′ UTR variants

Chuzhanova, Nadia; Cooper, David Neil; Férec, Claude; Chen, Jian‐Min

doi:10.1007/s11568-006-9000-3

Cited by 7 publications

(2 citation statements)

References 39 publications

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“…As previously reported, miRNAs modulated their biological functions through regulating target gene expression through complementarily binding to the 3′ UTR of mRNAs and miRNAs might play their roles by targeting multiple mRNAs (Chuzhanova et al, 2007). In the present report, using bioinformatic analysis, we showed that several genes were predicted to be potential targets of miR‐22, including SIRT1, NAT5, PTEN, HDAC4, and SRF.…”

Section: Discussionmentioning

confidence: 78%

Attenuation of MicroRNA‐22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy

Song

et al. 2012

Journal Cellular Physiology

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Cardiac hypertrophy, which is characterized by the enlargement of cell size, reactivation of fetal genes, remains one of the most important triggers to heart failure. Increasing evidence shows that microRNA (miRNA) is extensively involved in the pathogenesis of cardiac hypertrophy. But the effects of miRNAs on cardiomyocyte hypertrophy have not been completely solved yet. Here, we showed that a collection of miRNAs was aberrantly expressed in hypertrophic cardiomyocytes induced by phenylephrine (PE) or angiotensin II (Ang II). Among them, miR-22 was the most strikingly up-regulated miRNA. To investigate the role of miR-22 in hypertrophy, both over-expression and knock-down assays were performed on cardiomyocytes. The results showed that up-regulation of miR-22 significantly increased the cell size and markedly influenced the expression of hypertrophic markers, including induction of nppa and reduction of myh6. In contrast, reduction of miR-22 level attenuated either PE- or Ang II-induced hypertrophic reaction. Furthermore, several genes, including PTEN, were identified as potential targets of miR-22 by bioinformatic algorithms. Using luciferase analysis, miR-22 could significantly suppress the luciferase activity of reporter fused with 3' untranslated region of PTEN mRNA. Furthermore, up-regulation of miR-22 could suppress the protein level of PTEN and reduction of miR-22 level markedly increased the protein level of PTEN in cardiomyocytes by Western blot analysis, suggesting that the contribution of miR-22 to cardiomyocyte hypertrophy may be partially through targeting PTEN. Taken together, miRNAs were dynamically regulated in cardiomyocyte hypertrophy and attenuation of miR-22 in rat cardiomyocytes efficiently protected from hypertrophic effects through derepressing PTEN.

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Section: Discussionmentioning

confidence: 78%

Attenuation of MicroRNA‐22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy

Song

et al. 2012

Journal Cellular Physiology

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“…Generally, miRNAs modulate their biological functions through regulating target gene expression through complementarily binding to the 3′-UTR of mRNAs [28]. Each miRNA could repress possibly hundreds of transcripts, and there are interactions between miRNAs in the complex regulatory network of cardiac hypertrophy [29].…”

Section: Discussionmentioning

confidence: 99%

Attenuation of MicroRNA-495 Derepressed PTEN to Effectively Protect Rat Cardiomyocytes from Hypertrophy

Chen

2018

Cardiology

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Background: The effect of microRNA (miR)-495 on cardiomyocyte hypertrophy was explored by investigating the expression of proteins in the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway. Methods: The study used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) administration (60 mg/kg) for 2 weeks. Arterial wall thickness and right ventricular hypertrophy were examined by hematoxylin and eosin (HE) staining in the lungs and hearts. The expression level of miR-495 and PTEN was analyzed by quantitative (q)PCR and Western blotting. From the cellular level, we used loss-of-function approaches to investigate the functional roles of miR-495 in cardiac hypertrophy induced by angiotensin II (Ang II) with immunoﬂuorescence, qPCR, and Western blotting. Results: The results showed that upregulation of miR-495 markedly influenced the expression of hypertrophic markers, including the induction of nppa and the inhibition of myh6. In contrast, a reduction in the level of miR-495 attenuated an Ang II-induced hypertrophic reaction. Furthermore, PTEN was identified as a potential target of miR-495 by a bioinformatics algorithm. Luciferase analysis and Western blot analysis confirmed that the contribution of miR-495 to cardiomyocyte hypertrophy may partly be through targeting PTEN. Conclusions: Attenuation of miR-495 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy.

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Pathological Variations in 3′‐untranslated Regions of Human Genes

Pal¹,

Chatterjee²,

Berwal³

2010

Encyclopedia of Life Sciences

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The 3′‐untranslated regions (UTRs) of messenger ribonucleic acids (mRNAs) play a critical role in the stabilization, localization and translation of mRNAs. Mutations that disrupt functional elements of the 3′‐UTR of mRNAs such as polyadenylation signal, micro RNA (miRNA) target sites and AU‐rich elements lead to production of nonfunctional proteins or reduced amounts of functional proteins. Genetic variations in the 3′‐UTR are associated with disease risk or diseases such as spinocerebellar ataxia 8, Parkinson disease, breast cancer, atopic dermatitis, papillary thyroid carcinoma and many others. With the advent of genetic counselling and promise of personalized medicine, genetic variation in this region of mRNAs is the focus of intense research. Current research shows that this region is of immense significance in the context of translational research. Key concepts: 3′‐Untranslated regions (UTRs) are noncoding regions of mRNAs. The 3′‐UTR is delimited by stop codon (UAA or UAG or UGA) at the 5′ end and poly (A) tail at the 3′ end. Motifs like AU‐rich elements, polyadenylation signal, iron responsive elements and others are involved in mRNA stability, localization and translation. Mutations are changes in the DNA/gene of an organism which are heritable. Mutations in the AU‐rich elements lead to atypical stabilization of mRNA and associated diseases. Mutations that lead to abolition of canonical polyadenylation signal interfere with efficient transcription termination and polyadenylation of mRNA. Mutations in the 3′‐UTR may alter the binding sites of interacting miRNAs or proteins resulting in deregulation of mRNA translation. Single nucleotide polymorphisms (SNPs) in the 3′‐UTR are associated with individual's drug response and disease risk.

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Searching for potential microRNA-binding site mutations amongst known disease-associated 3′ UTR variants

Cited by 7 publications

References 39 publications

Attenuation of MicroRNA‐22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy

Attenuation of MicroRNA‐22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy

Attenuation of MicroRNA-495 Derepressed PTEN to Effectively Protect Rat Cardiomyocytes from Hypertrophy

Pathological Variations in 3′‐untranslated Regions of Human Genes

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