INTRODUCTION: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear. METHODS: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study. RESULTS: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants. DISCUSSION: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses. HIGHLIGHTS: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study.

• MeSH
• Alzheimerova nemoc * genetika   metabolismus   MeSH
• čichová sliznice metabolismus   MeSH
• epigenomika MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• látky znečišťující vzduch škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• mikro RNA metabolismus   genetika   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• výfukové emise vozidel * toxicita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3'-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.

• MeSH
• apoptóza * genetika   MeSH
• cyklin-dependentní kinasa 2 * metabolismus   genetika   MeSH
• kruhová RNA * genetika   metabolismus   MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory plic * genetika   patologie   metabolismus   MeSH
• nemalobuněčný karcinom plic * genetika   patologie   metabolismus   MeSH
• proliferace buněk * genetika   MeSH
• proteiny aktivující GTPasu genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• signální transdukce genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

DNA ligase 1 (LIG1) plays a key role in DNA synthesis and DNA damage repair pathways. LIG1 has been shown to be up-regulated in human non-small cell lung cancer (NSCLC); however, its role and molecular regulatory mechanism in NSCLC cell proliferation are still not fully understand. In this study, we aimed to explore the role of LIG1 and post-transcripional regulators in NSCLC. Utilizing bioinformatic tools and qRT-PCR, our investigation substantiated the up-regulation of LIG1 within NSCLC cell lines and tumour tissues. Remarkably, individuals exhibiting elevated levels of LIG1 had diminished survival rates. Functionally, the depletion of LIG1 inhibited cell proliferation and migration, contrasting with the increased proliferation and migration upon LIG1 over-expression. Prediction from the TargetScanHuman database and results of dual luciferase reporter assays indicated that miR-325 could directly bind to and negatively regulate LIG1. Moreover, our findings demonstrated that the mimicry of miR-325 decreased cell viability, whereas its inhibition correspondingly increased viability, indicative of the tumour-suppressive role of miR-325 through the down-regulation of LIG1. Collectively, our findings show that LIG1 could promote tumour progression and knockdown of LIG1 could exert suppressive effects on NSCLC. As the post-transcriptional factor of LIG1, miR-325 could negatively regulate the expression of LIG1 to inhibit tumour progression in vitro. These findings suggest that LIG1 and miR-325 might be potential therapeutic targets for NSCLC treatment.

• MeSH
• DNA-ligasa ATP * metabolismus   genetika   MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory plic * patologie   genetika   metabolismus   MeSH
• nemalobuněčný karcinom plic * genetika   patologie   metabolismus   MeSH
• pohyb buněk * MeSH
• proliferace buněk * MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

In mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. Lamin A KO manifested a more pronounced effect in SHSY5Y cells compared to A375 cells, evident by changes in cell morphology, increased cell proliferation, and oncogenic miRNA expression. Moreover, AGO fPAR-CLIP in Lamin A KO SHSY5Y cells revealed significantly reduced RNAi activity. Further exploration of the nuclear AGO interactome by mass spectrometry identified FAM120A, an RNA-binding protein and known interactor of AGO2. Subsequent FAM120A fPAR-CLIP, revealed that FAM120A co-binds AGO targets and that this competition reduces the RNAi activity. Therefore, loss of Lamin A triggers nuclear AGO2 translocation, FAM120A mediated RNAi impairment, and upregulation of oncogenic miRNAs, facilitating cancer cell proliferation.

• MeSH
• aktivní transport - buněčné jádro MeSH
• Argonaut proteiny * metabolismus   genetika   MeSH
• buněčné jádro * metabolismus   MeSH
• lamin typ A * metabolismus   genetika   MeSH
• lidé MeSH
• melanom genetika   metabolismus   patologie   MeSH
• mikro RNA * metabolismus   genetika   MeSH
• nádorové buněčné linie MeSH
• proliferace buněk * genetika   MeSH
• proteiny vázající RNA metabolismus   genetika   MeSH
• RNA interference * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

MicroRNA hsa-miR-29 was connected to a number of malignancies. Its target genes are many, among them Mcl-1 that is expressed in three possible isoforms, one of which is anti-apoptotic and another one pro-apoptotic. Ratio of these two isoforms appears to affect cell response to external stimuli. We have demonstrated that miR-29b enhanced etoposide toxicity in HeLa cell line by modulating this ratio of Mcl-1 isoforms. However, it is not known whether the described miR-29 effect is common to various cancer types or even have the opposite effect. This represents a significant problem for possible future applications. In this report, we demonstrate that miR-29b affects toxicity of 60 μM etoposide in cell lines derived from selected malignancies. The mechanism, however, differs among the cell lines tested. Hep G2 cells demonstrated similar effect of miR-29b on etoposide toxicity as was described in HeLa cells, i.e. modulation of Mcl-1 expression. Target protein down-regulated by miR-29b resulting in enhanced etoposide toxicity in Caco-2 cells was, however, Bcl-2 protein. Moreover, H9c2, Hek-293 and ARPE-19 cell lines selected as a representatives of non-malignant cells, showed no effect of miR-29b on etoposide toxicity. Our data suggest that miR-29b could be a common enhancer of etoposide toxicity in malignant cells due to its modulation of Bcl family proteins.

• MeSH
• antitumorózní látky fytogenní farmakologie   toxicita   MeSH
• apoptóza účinky léků   genetika   MeSH
• buňky Hep G2 MeSH
• Caco-2 buňky MeSH
• etoposid * toxicita   farmakologie   MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• protein MCL-1 * genetika   metabolismus   MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-β-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.

• MeSH
• fibroblasty metabolismus   MeSH
• fibróza * MeSH
• infarkt myokardu s elevacemi ST úseků metabolismus   patologie   genetika   MeSH
• infarkt myokardu * metabolismus   genetika   patologie   MeSH
• interleukin-1 receptor-like 1 protein metabolismus   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• myokard metabolismus   patologie   MeSH
• perikardiální tekutina * metabolismus   MeSH
• senioři MeSH
• transformující růstový faktor beta metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Pathogenesis of epilepsy involves dysregulation of the neurotransmitter system contributing to hyper-excitability of neuronal cells. MicroRNA (miRNAs) are small non-coding RNAs known to play a crucial role in post-transcriptional regulation of gene expression. METHODS: The present review was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, employing a comprehensive search strategy to identify and extract data from published research articles. Keywords suchas epilepsy, micro RNA (micro RNAs, miRNA, miRNAs, miR), neurotransmitters (specific names), and neurotransmitter receptors (specific names) were used to construct the query. RESULTS: A total of 724 articles were identified using the keywords epilepsy, microRNA along with select neurotransmitter and neurotransmitter receptor names. After exclusions, the final selection consisted of 17 studies, most of which centered on glutamate and gamma-aminobutyric acid (GABA) receptors. Singular studies also investigated miRNAs affecting cholinergic, purinergic, and glycine receptors. CONCLUSION: This review offers a concise overview of the current knowledge on miRNA-mediated regulation of neurotransmitter receptors in epilepsy and highlights their potential for future clinical application.

• MeSH
• epilepsie * genetika   metabolismus   MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• receptory neurotransmiterů * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

Cellular proteins and the mRNAs that encode them are key factors in oocyte and sperm development, and the mechanisms that regulate their translation and degradation play an important role during early embryogenesis. There is abundant evidence that expression of microRNAs (miRNAs) is crucial for embryo development and are highly involved in regulating translation during oocyte and early embryo development. MiRNAs are a group of short (18-24 nucleotides) non-coding RNA molecules that regulate post-transcriptional gene silencing. The miRNAs are secreted outside the cell by embryos during preimplantation embryo development. Understanding regulatory mechanisms involving miRNAs during gametogenesis and embryogenesis will provide insights into molecular pathways active during gamete formation and early embryo development. This review summarizes recent findings regarding multiple roles of miRNAs in molecular signaling, plus their transport during gametogenesis and embryo preimplantation.

• MeSH
• asistovaná reprodukce * MeSH
• embryonální vývoj * genetika   MeSH
• gametogeneze genetika   MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• oocyty metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.

• MeSH
• extracelulární vezikuly * metabolismus   MeSH
• kruhová RNA genetika   metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• mezibuněčná komunikace MeSH
• mikro RNA genetika   metabolismus   MeSH
• nádorové mikroprostředí * MeSH
• nádory * patologie   genetika   metabolismus   MeSH
• RNA dlouhá nekódující genetika   MeSH
• RNA genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.

• MeSH
• apoptóza * účinky léků   MeSH
• buněčné linie keratinocytů HaCaT MeSH
• buněčné linie MeSH
• dospělí MeSH
• interleukin-17 metabolismus   MeSH
• jaderné proteiny metabolismus   genetika   MeSH
• keratinocyty * účinky léků   metabolismus   MeSH
• kyselina gallová * farmakologie   MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• pohyb buněk * účinky léků   MeSH
• proliferace buněk * účinky léků   MeSH
• proteiny buněčného cyklu * metabolismus   genetika   MeSH
• proteiny obsahující bromodoménu MeSH
• psoriáza * metabolismus   patologie   farmakoterapie   MeSH
• regulace genové exprese účinky léků   MeSH
• transkripční faktory * metabolismus   MeSH
• zánět * patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH