A blood based 12-miRNA signature of Alzheimer disease patients

Leidinger, Petra; Backes, Christina; Deutscher, Stephanie; Schmitt, Katja; Mueller, Sabine C.; Frese, Karen; Haas, Jan; Ruprecht, Klemens; Paul, Friedemann; Stähler, Cord; Läng, Christoph; Meder, Benjamin; Bartfai, Tamás; Meese, Eckart; Keller, Andreas

doi:10.1186/gb-2013-14-7-r78

Cited by 445 publications

(369 citation statements)

References 62 publications

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“…RNU48 which was established before as an appropriate endogenous control for blood cell-derived miRNAs was used for normalization (16,20). The following conditions were applied for all PCR reactions: 40 cycles of 95°C for 15 s and 60°C for 60 s. Data analysis was done using the ∆∆C T method for relative quantification as previously specified (21).…”

Section: Real-time Reverse Transcription (Rt)-pcrmentioning

confidence: 99%

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Roth

Keller

Hoheisel

et al. 2015

European Journal of Cancer

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Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3months and was compared to 20 LTS patients with a median OS of 55months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Here we characterized microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analyzed by next generation sequencing.The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS.Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal AUC above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time PCR in a validation cohort consisting of 20 STS and LTS patients.In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients.

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Section: Real-time Reverse Transcription (Rt)-pcrmentioning

confidence: 99%

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Roth

Keller

Hoheisel

et al. 2015

European Journal of Cancer

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“…Alzheimer hastalarında Let-7d-3p, miR-26a-5p, miR-112, miR-151a-3p, miR-161, miR-1285-5p ve miR-5010-3p tiplerinin ekspresyon düzeyleri yüksek iken, Let-7f-3p, miR-26b-5p, miR-103a-3p, miR-107, ve miR-532-5p tiplerinin ekspresyon düzeylerinin düşük olduğu rapor edilmiştir. Aynı zamanda Alzheimer'lı olguların miRNA ekspresyon düzeylerinin multipl skleroz, parkinson, majör depresif bozukluk, bipolar bozukluk ve şizofrenisi olan olgulardan farklı olduğu gösterilmiştir 59 . Romatoid artritin (RA) miRNA ile ilşkisi 2008 yılında 3 farklı çalışma ile gösterilmiştir.…”

Section: Mirna'ların Tıpta Kullanım Alanlarıunclassified

Bir Gen İfade Düzenleyicisi miRNA

Güzelgül¹,

Aksoy²

2015

Arşiv Kaynak Tarama Dergisi

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MicroRNAs (miRNA) binding to target mRNAs and having function in regulating gene expression are of 18-25 nucleotides in length and take place in the class of non-coding RNAs. Although aproximately 1900 human miRNA types have been identified so far, quite little is known about their biological functions. In some studies, it is shown that miRNA expression levels are important for many biological functions such as cell proliferation, differentiation, apoptosis and metabolism. Recent studies have pointed out that miRNAs have been used as diagnosis and prognosis biomarker in many human diseases including cancer, viral diseases, cardiovascular disorders and metabolic distrubance. Such as a miRNA type's regulating more than one mRNA expression levels, a mRNA level has been regulated by numbers of miRNA types. Since changing the expression level of a miRNA type effects the whole metabolism, it is required to have cell-specific miRNAs. In the event of cell type-specific miRNAs are having found, it is expected that the general metabolism is better understood and, moreover, miRNAs are used more effectively in diagnosis and treatment of diseases. Key words: Noncoding RNA, miRNA, Mrna ÖZET Hedef mRNA'lara bağlanarak gen ifadesinin düzenlenmesinde işlev gören mikroRNA'lar (miRNA) 18-25 nükleotit uzunluğunda olup kısa kodlanmayan RNA sınıfında yer almaktadırlar. İnsanlarda yaklaşık 1900 miRNA tipi tanımlanmış olmasına rağmen şimdiye kadar biyolojik işlevleri hakkında bilinenler oldukça azdır. Bazı çalışmalarda hücrelerin proliferasyon, farklılaşma, apoptozis ve metabolizma gibi biyolojik işlevlerdemiRNA'ların ekspresyon seviyelerinin önemli olduğu gösterilmiştir. Son zamanlardaki çalışmalarda miRNA'ların kanser, viral hastalıklar, kardiovasküler hastalıklar ve metabolik bozuklukları da içine alan birçok hastalıkta tanı ve prognozda kullanılabileceği belirtilmiştir.

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“…Entretanto, muito dos fundamentos de biologia molecular já oferecem princípios sufi cientes para deduções importantes a respeito do assunto como a sequência de eventos envolvidos na regulação da expressão gênica em processos neuronais, tema hoje recorrente nas neurociências. Sabe-se, por exemplo, que a desregulação da expressão de microRNAs (miRNA) pode estar associada a disfunções neurológicas importantes, tal como o Alzheimer (FAGHIHI et al, 2010), tornando possível, inclusive, a prévia quantifi cação sérica de determinado micro-RNA envolvido nessa doença (LEIDINGER et al, 2013).…”

Section: Introductionunclassified

Da membrana ao núcleo: mecanismos moleculares de armazenamento da memória

Nunes

Queiroz

2018

Univ. Ci. Saúde

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Da membrana ao núcleo: mecanismos moleculares de armazenamento da memória* From membrane to nucleus: molecular mechanisms of memory storage ResumoOs estudos relacionados ao armazenamento de memória têm apresentado notáveis avanços em sua abordagem molecular. Enzimas chaves desse processo, tais como a proteína cinase A (PKA) e a proteína cinase C (PKC), bem como fatores de transcrição como a CREB-1 e a CREB-2, participam da plasticidade neuronal de consolidação da memória. A bibliografia deste trabalho conta com alguns dos mais avançados estudos relacionados à transdução de sinal em circuitos neuronais simples. As pesquisas se pautam em duas modalidades de armazenamento convencionadas: facilitação de curta duração (STF) e facilitação de longa duração (LTF), cada uma apresentando seus mecanismos particulares. A facilitação de duração média (ITF) também é mencionada. O objetivo do trabalho, portanto, é o de apresentar, de maneira sistemática, a cadeia de eventos moleculares e celulares que acompanham o armazenamento da memória implícita em suas diferentes durações. Em conclusão, os avanços da biologia molecular prometem fornecer perspectivas cada vez mais íntimas dos mecanismos que governam as funções mentais, especialmente a memória. Palavras-chave: AMPc. PKA. CREB. Transcrição. Plasticidade sináptica. Aplysia. AbstractThe studies related to memory storage have being noticing advances at the molecular issue. Key enzymes of this process, such as protein kinase A (PKA) and protein kinase C (PKC), as well as transcription factors like CREB-1 and CREB-2, participate of the neuronal plasticity of memory consolidation. The bibliography of the present study count with some of the most advanced studies related to sign transduction into simple neuronal circuits. The studies are guided in two modes of storage: short-term facilitation (STF) and long-term facilitation (LTF), each one presenting particular mechanisms. Intermediate-term facilitation (ITF) is also mentioned. This study, therefore, is to present, on a systematic perspective, the molecular and cellular chains events that underlie the storage of implicit memory at different stages. To conclude, the advances in molecular biology are promising to provide intimate approaches of the mechanisms that govern our mental functions, especially memory.

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A blood based 12-miRNA signature of Alzheimer disease patients

Cited by 445 publications

References 62 publications

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Bir Gen İfade Düzenleyicisi miRNA

Da membrana ao núcleo: mecanismos moleculares de armazenamento da memória

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