MicroRNA-298 and MicroRNA-328 Regulate Expression of Mouse β-Amyloid Precursor Protein-converting Enzyme 1

Boissonneault, Vincent; Plante, Isabelle; Rivest, Serge; Provost, Patrick

doi:10.1074/jbc.m807530200

Cited by 294 publications

(228 citation statements)

References 43 publications

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“…hsa-miR-298 has been shown to target beta-amyloid precursor protein-converting enzyme mRNA and on this basis is predicted to have a role in Alzheimer's disease. 37,38 hsa-miR-346 may function in the differentiation of mesenchymal stem cells from bone marrow by targeting the leukaemia inhibitory factor. 39 Our data indicate that these miRNAs are also associated with prostate cancer and could be useful circulating markers of this disease.…”

Section: Discussionmentioning

confidence: 99%

Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

Selth

Townley

Gillis

et al. 2011

Intl Journal of Cancer

176

155

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Circulating microRNAs (miRNAs) are emerging as useful non-invasive markers of disease. The objective of this study was to use a mouse model of prostate cancer as a tool to discover serum miRNAs that could be assessed in a clinical setting. Global miRNA profiling identified 46 miRNAs at significantly altered levels (p 0.05) in the serum of TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice with advanced prostate cancer compared to healthy controls. A subset of these miRNAs with known human homologues were validated in an independent cohort of mice and then measured in serum from men with metastatic castration-resistant prostate cancer (mCRPC; n 5 25) or healthy men (n 5 25). Four miRNAs altered in mice, mmumiR-141, mmu-miR-298, mmu-miR-346 and mmu-miR-375, were also found to be at differential levels in the serum of men with mCRPC. Three of these (hsa-miR-141, hsa-miR-298 and hsa-miR-375) were upregulated in prostate tumors compared with normal prostate tissue, suggesting that they are released into the blood as disease progresses. Moreover, the intra-tumoral expression of hsa-miR-141 and hsa-miR-375 were predictors of biochemical relapse after surgery. This study is the first to demonstrate that specific serum miRNAs are common between human prostate cancer and a mouse model of the disease, highlighting the potential of such models for the discovery of novel biomarkers.Prostate cancer is the most commonly diagnosed non-skin malignancy in men in Western countries, constituting up to 25% of all male cancer diagnoses and 9% of cancer deaths among men in the USA and Europe. 1,2 The widespread use of serum prostate specific antigen (PSA) testing along with increasing public awareness of prostate cancer has resulted in a significant increase in the proportion of patients with clinically localized tumors at the time of diagnosis who likely will not die of the disease. 3 Localized prostate cancers exhibit high levels of genetic, biological and clinical heterogeneity, 4,5 and current prognostic tools (based upon clinicopathologic parameters) are imperfect predictors of disease course. New molecular markers are urgently required to better predict the likely outcome and behavior of individual cancers. microRNAs (miRNAs) are small RNA molecules of 21-23nt that bind with imperfect complementarity to sequences in specific mRNA targets and typically silence their expression by translational inhibition or mRNA decay. miRNAs are estimated to regulate the expression of greater than 60% of all protein-coding genes 6 and, as such, play vital roles in all aspects of normal physiology. Given their biological importance, it is not surprising that miRNA expression is frequently dysregulated in human cancer. 7 Accumulating evidence suggests that miRNAs can contribute to tumorigenesis either by directly modulating oncogenic or tumor suppressor pathways (oncomirs and tumor suppressor miRNAs, respectively) and/or being regulated by oncogenes or tumor suppressor genes. 8 Several characteristics of miRNAs make them ideal biomarkers for...

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Section: Discussionmentioning

confidence: 99%

Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

Selth

Townley

Gillis

et al. 2011

Intl Journal of Cancer

176

155

View full text Add to dashboard Cite

show abstract

“…We also observed a loss of correlation between BACE1 mRNA and protein levels in the hippocampus of APP Swe /PS1 mice (Boissonneault et al, 2009), a murine model of AD. Consistent with an impairment of miRNA-mediated regulation of BACE1 mRNA translation, we were able to validate this hypothesis and demonstrate a role for two miRNAs, i.e.…”

Section: Micrornas and Alzheimer's Diseasementioning

confidence: 65%

“…The ensuing deregulation of mRNA translation may then lead to misexpression, i.e. either downregulated or upregulated expression, of a specific protein and provoke the development of a disease (Perron et al, 2007), which may be the case of the β-amyloid precursor protein (APP)-converting enzyme (BACE) in Alzheimer's disease (AD) (see section 5) (Boissonneault et al, 2009). Hence the relevance of using miRNAs as biomarkers and therapeutic targets/drugs in human diseases affecting major organs, such as the brain.…”

Section: Micrornas In Health and Diseasementioning

confidence: 99%

“…mmu-miR-298 and mmu-miR-328, in the regulation of BACE1 expression in transiently transfected murine neuronal N2a cells in culture. It is relevant to note that both Drosha and Dicer mRNA levels were enriched in the hippocampus and the dentate gyrus of mouse brain (Boissonneault et al, 2009), which are also the regions that are the most severely affected by Aβ deposits in AD. The concept of a link between dysfunctional miRNA regulation of BACE1 expression and AD is supported further by the detection of miR-298 and miR-328 in the hippocampus of APP Swe /PS1 mice, as well as by their decreased expression levels during aging (Boissonneault et al, 2009).…”

Section: Micrornas and Alzheimer's Diseasementioning

confidence: 99%

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MicroRNAs as a molecular basis for mental retardation, Alzheimer's and prion diseases

Provost¹

2010

Brain Research

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MicroRNAs (miRNAs) are small, ~21-to 23-nucleotide (nt) non-coding RNA species that act as key regulators of gene expression along a central and well-defined cellular process known as RNA silencing, and involving the recognition and translational control of specific messenger RNA (mRNAs). Generated through the well-orchestrated and sequential processing of miRNA precursor molecules, mature miRNAs are subsequently incorporated into miRNA-containing ribonucleoprotein effector complexes to regulate mRNA translation through the recognition of specific binding sites of imperfect complementarity located mainly in the 3′ untranslated region. Predicted to regulate up to 90% of the genes in humans, miRNAs may thus control cellular processes in all cells and tissues of the human body. Likely to play a central role in health and disease, a dysfunctional miRNA-based regulation of gene expression may represent the main etiologic factor underlying diseases affecting major organs, such as the brain. In this review article, the molecular mechanisms underlying the role and function of miRNAs in the regulation of genes involved in neurological and neurodegenerative diseases will be discussed, with a focus on the fragile X syndrome, Alzheimer's disease (AD) and prion disease.

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“…Therefore, diverse miRNA repertoires in the brain likely contribute to the dissimilarities between human and chimpanzee, arguing for a role of miRNA in brain evolution and function [14,15]. MicroRNAs have been identified as regulators of key genes involved in Alzheimer's Disease, including APP [16][17][18], BACE1 [19][20][21][22][23] and microtubule associated protein tau, MAPT [24][25][26]. In all these works changes of miRNA expression were corrrelated to AD pathology, without, however, to determine whether the dysregulation of these microRNAs is cause or consequence of the disease.…”

mentioning

confidence: 99%

Alzheim(i)R: MicroRNAs in Alzheimer’s Disease

Barbato¹

2014

J Cytol Histol

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MicroRNA-298 and MicroRNA-328 Regulate Expression of Mouse β-Amyloid Precursor Protein-converting Enzyme 1

Cited by 294 publications

References 43 publications

Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

MicroRNAs as a molecular basis for mental retardation, Alzheimer's and prion diseases

Alzheim(i)R: MicroRNAs in Alzheimer’s Disease

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