MicroRNA
Dotaz
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sv.
- Konspekt
- Obecná genetika. Obecná cytogenetika. Evoluce
- NLK Obory
- genetika, lékařská genetika
- biologie
- MeSH
- antisense oligodeoxyribonukleotidy fyziologie genetika MeSH
- financování vládou MeSH
- genetická terapie MeSH
- lidé MeSH
- malá interferující RNA fyziologie genetika MeSH
- mikro RNA fyziologie genetika MeSH
- regulace genové exprese genetika imunologie MeSH
- RNA interference imunologie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: MicroRNAs (miRNA) are small non-coding RNAs that negatively regulate gene expression in a sequence- specific manner. Post-transcriptional silencing of target genes by miRNA occurs either by specific cleavage of homologous mRNA or by specific inhibition of protein synthesis. MiRNAs are essential regulators of various processes such as proliferation, differentiation, development, cell death and interaction between virus and host cell. AIM: The aim of this paper is to summarize the main findings from research on miRNA biogenesis, functionality and cancer relevance. METHOD: A narrative literature review of all of the relevant papers known to the authors was conducted. RESULTS: Several human diseases including cancer are associated with aberrant regulation of miRNAs expression or deficiency in miRNA biogenesis. Analysis of miRNA expression signatures can serve as a valuable tool for cancer classification, diagnostics and prediction of tumor behavior. CONCLUSIONS: There has been demonstrated a possibility to use these microRNA signatures for a specific cancer classification with potential predictive and therapeutic value. The known data provide evidence that microRNAs may open new ways for cancer diagnosis, prognosis estimation and therapy.
RNA interferencia bola popísaná ako proces post-transkripčného utlmovania génovej expresie, sprostredkovaný dvojreťazcovými molekulami RNA, a ako obranný mechanizmus bunky proti vírusom a transpozónom. Porozumenie mechanizmu RNA interferencie umožnilo jeho experimentálne využitie na cielené utlmovanie génovej expresie a prinieslo zaujímavé informácie o spojitosti RNA interferencie a niektorých ochorení. Cielené utlmovanie génovej expresie umožňuje jednak detailné štúdium funkcie jednotlivých génov a stáva sa jedným z nových a nádejných prístupov pre génovú terapiu.
Nature genetics ; suppl., vol. 38, June 2006
36 s. : il., grafy ; 30 cm
2nd ed. 2 sv. : il., tab. ; 29 cm
OBJECTIVE: Polycythemia vera (PV) is a myeloproliferative disorder, arising from the acquired mutation(s) of a hematopoietic stem cell. The JAK2 V617F somatic mutation is found in most PV patients; however, it is not the disease-initiating mutation. Because microRNAs (miRNAs) play a regulatory role in hematopoiesis, we studied miRNA expressions in PV and normal erythropoiesis. METHODS: Peripheral blood mononuclear cells were cultured in a three-phase liquid system resulting in synchronized expansion of erythroid progenitors. Using gene-expression profiling by CombiMatrix MicroRNArray, we searched for PV-specific changes at days 1, 14, and 21. Twelve miRNA candidates were then reevaluated by quantitative real-time polymerase chain reaction in a larger number of samples obtained from progenitors at the same stage of differentiation. RESULTS: A significant difference in miR-150 expression was found in PV. In normal erythropoiesis, three expression patterns of miRNAs were observed: progressive downregulation of miR-150, miR-155, miR-221, miR-222; upregulation of miR-451, miR-16 at late stages of erythropoiesis; and biphasic regulation of miR-339, miR-378. The miR-451 appears to be erythroid-specific. CONCLUSIONS: We identified the miRNAs with regulated expression in erythropoiesis; one appeared to be PV-specific. Their miRNA expression levels define early, intermediate, and late stages of erythroid differentiation. The validity of our findings was confirmed in nonexpanded peripheral blood cells.
- MeSH
- buněčná diferenciace genetika MeSH
- časové faktory MeSH
- erytroidní prekurzorové buňky MeSH
- erytropoéza * genetika MeSH
- kultivované buňky MeSH
- leukocyty mononukleární MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- polycythaemia vera * genetika MeSH
- regulace genové exprese u nádorů * MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- stanovení celkové genové exprese MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- Research Support, N.I.H., Extramural MeSH
OBJECTIVES: Development and metastases of colorectal cancer (CRC) are characterized by multiple genetic alterations. MicroRNAs (miRNAs) are endogenously expressed regulatory noncoding RNAs. Previous, mainly preclinical studies showed altered expression levels of several miRNAs in CRC. METHODS: In our study, the expression levels of miR-21, miR-31, miR-143 and miR-145 in 29 primary colorectal carcinomas and 6 non-tumor adjacent tissue specimens were examined by real-time polymerase chain reaction. miRNA expression levels were also correlated with commonly used clinicopath-ologic features of CRC. RESULTS: Expression levels of analyzed miRNAs significantly differed among tumors and adjacent non-tumor tissues: miR-21 (p = 0.0001) and miR-31 (p = 0.0006) were upregulated, and miR-143 (p = 0.011) and miR-145 (p = 0.003) were downregulated in tumors. For the first time, a high expression of miR-21 was associated with lymph node positivity (p = 0.025) and the development of distant metastases (p = 0.009) in CRC patients. Thus, expression of miR-21 correlated with CRC clinical stage (p = 0.032). Furthermore, tumors >50 mm in maximal tumor diameter were characterized by lower expression of miR-143 (p = 0.006) and miR-145 (p = 0.003). We found no correlation between analyzed miRNAs and serum levels of carcinoembryonic antigen. CONCLUSION: Our results suggest possible roles of miR-21, miR-31, miR-143 and miR-145 in CRC. (c) 2008 S. Karger AG, Basel
- MeSH
- financování organizované MeSH
- klinické zkoušky jako téma MeSH
- kolorektální nádory genetika patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
Představy o patogenezi a prognostických znacích chronické lymfatické leukemie (CLL) se v posledním desetiletí výrazně změnily. Objevilo se mnoho nových prognostických faktorů (ZAP-70, ATM, cytogenetická, molekulárně genetická a funkční analýza genu p53; mutační stav IgVH, microRNA). Na druhou stranu indikace pro zahájení terapie se u CLL stále opírá o konvenční hematologické a klinické nálezy i přesto, že máme k dispozici nové a účinné léčebné postupy. Přesná role nových prognostických znaků CLL tak stále zůstává nejasná. Náš přehled se zaměřuje na čerstvé pokroky v diagnostice a stanovení prognózy pacientů s CLL s důrazem na jejich důsledky pro klinický přístup k nemocným s CLL. Stratifikace pomocí nových biologických prognostických znaků může vést k vylepšení péče o nemocné a ukazuje směr budoucího klinického výzkumu.
The opinions about the pathogenesis and prognostic factors of chronic lymphocytic leukemia (CLL) have undergone significant changes over the past decade and a variety of new prognostic factors have been discovered (ZAP-70; ATM; cytogenetic, molecular genetic and functional analysis of p53; a mutational status of IgVH; microRNA). On the other hand, however, indication for the start of therapy continues to be based on the conventional hematological and clinical findings, while a range of new and effective therapeutic procedures is now used in the CLL therapy. The exact current role of the new prognostic markers of CLL therefore remains undefined. This review focuses on the most recent advances in the diagnostic and prognostic examination of patients with CLL, with particular emphasis on their implications in clinical management. Risk stratification using biological prognostic markers can improve current patient care and direct future clinical research.
Pediatric research, ISSN 0031-3998 vol. 61, no. 5/Part 2, May 2007
75 s. : il., tab. ; 28 cm
- MeSH
- dítě MeSH
- endokrinní disruptory MeSH
- epigeneze genetická MeSH
- genomový imprinting MeSH
- metylace DNA MeSH
- mikro RNA MeSH
- oprava chybného párování bází DNA MeSH
- vývojová biologie MeSH
- výzkum MeSH
- Check Tag
- dítě MeSH
- Publikační typ
- sborníky MeSH
