Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor and putative biomarker of solid tumours. Recently, we have revealed a variety of HNF1B mRNA alternative splicing variants (ASVs) with unknown, but potentially regulatory, functions. The aim of our work was to quantify the most common variants and compare their expression in tumour and non-tumour tissues of the large intestine, prostate, and kidney. The HNF1B mRNA variants 3p, Δ7, Δ7-8, and Δ8 were expressed across all the analysed tissues in 28.2-33.5%, 1.5-2%, 0.8-1.7%, and 2.3-6.9% of overall HNF1B mRNA expression, respectively, and occurred individually or in combination. The quantitative changes of ASVs between tumour and non-tumour tissue were observed for the large intestine (3p, Δ7-8), prostate (3p), and kidney samples (Δ7). Decreased expression of the overall HNF1B mRNA in the large intestine and prostate cancer samples compared with the corresponding non-tumour samples was observed (p = 0.019 and p = 0.047, respectively). The decreased mRNA expression correlated with decreased protein expression in large intestine carcinomas (p < 0.001). The qualitative and quantitative pattern of the ASVs studied by droplet digital PCR was confirmed by next-generation sequencing, which suggests the significance of the NGS approach for further massive evaluation of the splicing patterns in a variety of genes.

• MeSH
• alternativní sestřih * MeSH
• hepatocytární jaderný faktor 1-beta genetika   metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory genetika   metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• protein - isoformy MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• RNA nádorová genetika   metabolismus   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Epitachophoresis is a novel next generation extraction system capable of isolating DNA and RNA simultaneously from clinically relevant samples. Here we build on the versatility of Epitachophoresis by extracting diverse nucleic acids ranging in lengths (20 nt-290 Kbp). The quality of extracted miRNA, mRNA and gDNA was assessed by downstream Next-Generation Sequencing.

• MeSH
• DNA nádorová analýza   chemie   izolace a purifikace   MeSH
• fixace tkání MeSH
• kolorektální nádory genetika   patologie   MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• nádory plic genetika   patologie   MeSH
• RNA nádorová analýza   chemie   izolace a purifikace   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.

• MeSH
• autofagie * MeSH
• genové regulační sítě * MeSH
• lidé MeSH
• protoonkogenní proteiny c-myc genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• RNA nádorová genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

NF-κB is activated in a variety of human cancers. However, its role in osteosarcoma (OS) remains unknown. Here, we have elucidated the implication of NF-κB in the oncogenic phenotype of OS tumor cells. We reported that activation of NF-κB was a common event in the human OS. Inhibition of NF-κB using inhibitor Bay 11-7085 repressed proliferation, survival, migration, and invasion but increased apoptosis in 143B and MG63 OS cells, indicating that NF-κB is critically implicated in the oncogenesis of OS. Notably, Bay 11-7085 not only inactivated NF-κB but also reduced the phosphorylation of AKT via its induction of PTEN, suggesting the existence of a novel NF-κB/PTEN/PI3K/AKT axis. In vivo, Bay 11-7085 suppressed tumor growth in the bone by targeting NF-κB and AKT. Interestingly, combined treatment with Bay 11-7085 and the PI3K inhibitor, LY294002, triggered an augmented antitumor effect. Our results demonstrate that NF-κB potentiates the growth and aggressiveness of OS. Pharmacological inhibition of NF-κB represents a promising therapy for the treatment of OS.

• Klíčová slova
• Bay 11-7085 Sigma-Aldrich,
• MeSH
• cílená molekulární terapie MeSH
• dimethylsulfoxid terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední NOD MeSH
• nádorové buňky kultivované účinky léků   MeSH
• NF-kappa B účinky léků   MeSH
• nitrily farmakologie   terapeutické užití   MeSH
• osteosarkom * farmakoterapie   genetika   patologie   MeSH
• polymerázová řetězová reakce metody   MeSH
• protoonkogenní proteiny c-akt antagonisté a inhibitory   genetika   metabolismus   MeSH
• RNA nádorová izolace a purifikace   účinky léků   MeSH
• sulfony farmakologie   terapeutické užití   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

Cellular mechanisms that safeguard genome integrity are often subverted in cancer. To identify cancer-related genome caretakers, we employed a convergent multi-screening strategy coupled to quantitative image-based cytometry and ranked candidate genes according to multivariate readouts reflecting viability, proliferative capacity, replisome integrity, and DNA damage signaling. This unveiled regulators of replication stress resilience, including components of the pre-mRNA cleavage and polyadenylation complex. We show that deregulation of pre-mRNA cleavage impairs replication fork speed and leads to excessive origin activity, rendering cells highly dependent on ATR function. While excessive formation of RNA:DNA hybrids under these conditions was tightly associated with replication-stress-induced DNA damage, inhibition of transcription rescued fork speed, origin activation, and alleviated replication catastrophe. Uncoupling of pre-mRNA cleavage from co-transcriptional processing and export also protected cells from replication-stress-associated DNA damage, suggesting that pre-mRNA cleavage provides a mechanism to efficiently release nascent transcripts and thereby prevent gene gating-associated genomic instability.

• MeSH
• aktivní transport - buněčné jádro MeSH
• DNA nádorová genetika   metabolismus   MeSH
• HeLa buňky MeSH
• heteroduplexy nukleové kyseliny genetika   metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• messenger RNA biosyntéza   genetika   MeSH
• nádory genetika   metabolismus   MeSH
• nestabilita genomu * MeSH
• polyadenylace MeSH
• poškození DNA * MeSH
• prekurzory RNA biosyntéza   genetika   MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• replikace DNA * MeSH
• RNA nádorová biosyntéza   genetika   MeSH
• štěpení RNA * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Multiple myeloma is the second most common hematological malignancy characterized by focal lesions of malignant plasma cells in the bone marrow. These lesions contain subclones that directly influence survival of patients. Bone marrow biopsies are single-site biopsies and thus cannot contain all information about the tumor. In contrast, liquid biopsies analyze circulating cells and molecules that are secreted from all sites of the tumor. Long noncoding RNA molecules are one class of these molecules. We performed a two-phase biomarker study investigating lncRNA expression profiles in exosomes of peripheral blood serum of newly diagnosed multiple myeloma (MM) patients, monoclonal gammopathy of undetermined significance (MGUS) patients in comparison with healthy donors (HD). Surprisingly, this analysis revealed dysregulation of only one exosomal lncRNA PRINS in MM vs HD. Overall, MM and MGUS patients were distinguished from HD with sensitivity of 84.9% and specificity of 83.3%. Our study suggests a possible diagnostic role for exosomal lncRNA PRINS in monoclonal gammopathies patients.

• MeSH
• dospělí MeSH
• exozómy metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mnohočetný myelom * krev   diagnóza   mortalita   MeSH
• přežití bez známek nemoci MeSH
• RNA dlouhá nekódující krev   MeSH
• RNA nádorová krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

• MeSH
• dítě MeSH
• juvenilní myelomonocytární leukemie genetika   metabolismus   patologie   MeSH
• lidé MeSH
• předškolní dítě MeSH
• regulace genové exprese u leukemie * MeSH
• RNA dlouhá nekódující biosyntéza   genetika   MeSH
• RNA nádorová biosyntéza   genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.

• MeSH
• DNA nádorová * genetika   metabolismus   MeSH
• epigeneze genetická * MeSH
• epigenomika normy   MeSH
• lidé MeSH
• nádory * genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• RNA nádorová * genetika   metabolismus   MeSH
• stanovení celkové genové exprese metody   normy   MeSH
• transkriptom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

Lung cancer is one of the leading causes of cancer-related deaths. It is diagnosed mostly at the locally advanced or metastatic stage. Recently, micro RNAs (miRs) and their distribution in circulation have been implicated in physiological and pathological processes. In this study, miR-126 was evaluated in serum, exosome and exosome-free serum fractions in non-small cell lung cancer (NSCLC) patients at early and advanced stages, and compared with healthy controls. Down-regulation of miR-126 was found in serum of advanced stage NSCLC patients. In healthy controls, circulating miR-126 was equally distributed between exosomes and exosome-free serum fractions. Conversely, in both early and advanced stage NSCLC patients, miR-126 was mainly present in exosomes. Different fractions of miR-126 in circulation may reflect different conditions during tumour formation. Incubation of exosomes from early and advanced NSCLC patients induced blood vessel formation and malignant transformation in human bronchial epithelial cells. On the other hand, exosome-enriched miR-126 from normal endothelial cells inhibited cell growth and induces loss of malignancy of NSCLC cells. These findings suggest a role of exo-miRs in the modulation of the NSCLC microenvironmental niche. Exosome-delivered miRs thus hold a substantial promise as a diagnostics biomarker as well as a personalized therapeutic modality.

• MeSH
• cirkulující mikroRNA krev   MeSH
• dospělí MeSH
• exozómy metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• nádorové biomarkery krev   MeSH
• nádorové mikroprostředí MeSH
• nádory plic krev   patologie   MeSH
• nemalobuněčný karcinom plic krev   patologie   MeSH
• RNA nádorová krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Úvod: Adjuvantní chemoterapie se stala nedílnou součástí radikálně operovaných pacientů s plicními karcinomy stadií 2, 3 a dále pak i 1B větších než 4 cm. Pro menší nálezy stadií 1B a stadium 1A nebyl pro celkovou populaci pacientů prokázán přínos této léčby. Nicméně je známo, že i zde není riziko recidivy onemocnění po chirurgickém odstranění nádoru zanedbatelné. Naším cílem bylo posoudit vztah exprese vybraných protein kódujících genů a mikroRNA k době do progrese onemocnění (DFI) a celkovému přežití (OS) pacientů s plicními adenokarcinomy nízkých stadií, a pokusit se tak najít možný marker rizika recidivy onemocnění a identifikovat pacienty, kteří by mohli mít prospěch z podání adjuvantní chemoterapie. Pacienti a metody: Naše studie zahrnovala 42 pacientů (31 mužů a 11 žen, vyjma 4 nemocných byli všichni kuřáci či bývalí kuřáci) s radikálně operovaným plicním adenokarcinomem stadií 1A a 1B bez adjuvantně podávané chemoterapie. Exprese vybraných mRNA a miRNA byla měřena pomocí kvantitativní RT PCR v nádorové tkáni, získané makrodisekcí z formalinem fixovaných parafínových bločků (FFPE) bioptované tkáně. Byl analyzován vztah mezi hladinou genové exprese vybraných mRNA a miRNA a DFI a OS. Výsledky: Z celkového setu mRNA a mikroRNA našeho zájmu jsme neprokázali žádný statisticky významný vztah mezi jejich expresí a DFI/OS. Pouze u podskupiny kuřáků/exkuřáků byl prokázán signifikantní vztah mezi hladinou mRNA BRCA1 a OS. Závěr: V rutinně připravovaných FFPE nádorových vzorcích jsme prokázali vztah mezi kratším OS a hladinou BRCA1 u podskupiny kuřáků/exkuřáků. Tento výsledek je však vzhledem k malé skupině souboru nutné potvrdit dalšími studiemi.

Introduction: Adjuvant chemotherapy has become an integral part of treatment of radically operated patients with lung cancer stages 2, 3 and IB larger than 4 cm. For smaller tumors (stages IB and lA), the benefits of this treatment have not been demonstrated for the overall patient population. However, it is known that the risk of disease recurrence following surgical removal of the tumor is not negligible. The aims were to assess the relationship between expression of selected protein-coding genes and microRNAs and disease-free interval (DFI) and overall survival (OS) in patients with early-stage lung adenocarcinoma cind to try to find a possible marker of risk of disease recurrence an( id thus identify the patient population that might benefit from adjuvant chemotherapy. Patients and Methods: The study included 42 patients (31 males and 11 females; all but 4 patients were smokers or ex-smokers) with radically operated stage lA and IB lung adenocarcinoma not receiving adjuvant chemotherapy. Expression of selected mRNAs and miRNAs was measured by quantitative RT-PCR in tumor tissues obtained by macrodissection from formalin-fixed paraffin-embedded (FFPE) tissue biopsies. The relationships between gene expression levels of selected mRNAs and miRNAs and DFI and OS was analyzed. Results: In the entire set of mRNAs cind microRNAs of interest, no statistically significant relationship was found between their expression and DFI or OS. In the subgroup of smokers or ex-smokers only, a significant relationship was demonstrated between the mRNA level of BRCAl and OS. Conclusion: Using routinely prepared FFPE tumor samples, a relationship between shorter OS and the level of BRCAl was demonstrated in the subgroup of smokers or ex-smokers. Given the small sample size, however, the results need to be confirmed by further studies.

• MeSH
• adenokarcinom MeSH
• analýza přežití MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• nádorové biomarkery MeSH
• nádory plic * diagnóza   genetika   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• RNA nádorová analýza   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH