Nucleosides, Nucleotides & Nucleic Acids最新文献

In recent years, the incidence of cervical cancer has been on the rise, making it imperative to search for targeted therapeutic tumor-associated biomarkers. PCED1B-AS1 regulates gene expression and affects cell proliferation and differentiation in tumors. However, its function and potential mechanisms in cervical cancer remain unclear. The expression of PCED1B-AS1 in cervical cancer and adjacent tissues was detected by qRT-PCR, and its clinical significance was analyzed by chi-square test and Cox model. The interaction between PCED1B-AS1 and miR-361-3p was verified by ENCORI database, and luciferase reporter assay was used to verify the interaction. The CCK-8 and Transwell assays were used to evaluate their effects on cervical cancer cell function. The expression of PCED1B-AS1 in cervical cancer tissues was significantly higher than that in adjacent tissues, and was significantly correlated with tumor grade, stage, and FIGO classification. The upregulation of PCED1B-AS1 can predict adverse prognosis in cervical cancer patients, and the expression of PCED1B-AS1 is negatively correlated with the expression of miR-361-3p. Silencing PCED1B-AS1 significantly inhibited the growth, migration, and invasion of CaSki and HeLa cells, while inhibition of miR-361-3p could diminish this effect. PCED1B-AS1 is significantly upregulated in cervical cancer tissue, and the regulatory axis formed with miR-361-3p may be involved in tumor progression. Importantly, the high expression of PCED1B-AS1 is significantly associated with poor prognosis in patients, suggesting that it not only serves as a novel molecular biomarker for the diagnosis of cervical cancer but may also provide potential intervention targets for the development of targeted therapeutic strategies.

Non-small cell lung cancer (NSCLC) poses a severe challenge to global public health safety. This research aimed at exploring the correlation between serum miR-892b and serum tumor marker (TMs) in NSCLC patients, and examining its significance in clinical diagnosis. For this research, 114 NSCLC patients and 108 healthy volunteers were enrolled. Quantitative reverse transcription PCR was employed to detect the expression of miR-892b in serum and tissues of NSCLC patients. The combined diagnostic value of miR-892b and TMs (carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), neuron-specific enolase (NSE) and carbohydrate antigen 125 (CA125)) in NSCLC was analyzed by receiver operating characteristic curve. The chi-square test was conducted to analyze the correlations between miR-892b and clinical data. Multivariate logistic regression analysis was conducted to pinpoint independent risk factors for NSCLC. MiR-892b was significantly elevated in the serum and tissues of NSCLC patients. Serum CEA, CYFRA21-1, NSE and CA125 levels were significantly higher than those of the control group. The combined diagnosis of miR-892b and TMs had higher diagnostic efficacy. High-expression miR-892b was strongly correlated with tumor-node-metastasis stage, tumor differentiation, lymph node metastasis stage, CEA, CYFRA21-1, NSE, and CA125. MiR-892b and TMs were identified as independent risk factors influencing NSCLC. MiR-892b may be a promising biomarker for NSCLC, which is important for enhancing the early diagnosis of NSCLC.

To elucidate the prognostic significance and the underlying mechanism of action of circ_0005728 in patients diagnosed with cervical cancer (CCA). Intraoperative CCA and adjacent precancerous tissues from 208 patients were meticulously preserved at -80 °C. Kaplan-Meier survival curves were generated during a comprehensive 5-year postoperative follow-up. Cox analyses predicted the factors influencing prognostic progression in CCA patients. RT-qPCR detected the expression of circ_0005728. CCK8 and transwell observed cell proliferation, migration, and invasion. Flow cytometry recorded apoptotic changes. Dual luciferase reporter assay and RNA precipitation verified the interactions between circ_0005728 and miR-370-3p. High levels of circ_0005728 were observed in CCA tissues and cells. Elevated circ_0005728 expression and lymph node metastasis emerged as independent prognostic factors associated with poor outcomes in CCA patients. After silencing circ_0005728, cell functions were diminished and apoptosis increased. In addition, miR-370-3p is a downstream target gene of circ_0005728. Low expression of miR-370-3p was present in CCA tissues and was negatively correlated with circ_0005728 expression. The use of miR-370-3p inhibitor was able to induce cell proliferation, reduce apoptosis, and resist the reduction of cell migration and invasion caused by transfection of si-circ_0005728. The elevated expression of circ_0005728 in CCA patients was associated with prognostic mortality outcomes. circ_0005728 exerts its influence by targeting miR-370-3p, thereby enhancing the functional capabilities of CCA cells, diminishing apoptosis, and facilitating the malignant progression of CCA.

MicroRNAs (miRNAs) have been a popular subject of tumor research including pancreatic carcinoma (PC). MicroRNA-34c-3p (miR-34c-3p) is a member of miR-34c cluster, which is strongly associated with tumorigenesis. Nonetheless, miR-34c-3p has not been explored in PC. MiR-34c-3p was taken as a target to explore its current clinical significance and related molecular mechanisms in PC. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to monitor miR-34c-3p and FOXO3 level in tissues and PC cells. Dual-Luciferase reporter assay was utilized to verifying the relationship between miR-34c-3p and FOXO3. Cell Counting Kit-8 (CCK-8) and Transwell assay were applied to detect cell proliferation, migration and invasion. MiR-34c-3p was markedly elevated in PC tissues and closely related with lymph node metastasis, post-treatment nodal margin category and degree of differentiation. MiR-34c-3p upregulation could predict poorer prognosis and higher risk of PC patients. In PC cells, overexpression of miR-34c-3p enhanced cell proliferation, migration and invasion. Moreover, miR-34c-3p negatively regulated FOXO3 to promote cellular processes. High level of miR-34c-3p is a poor prognostic factor for PC patients and miR-34c-3p promotes tumor progression by negatively regulating FOXO3.

Lung Cancer is the leading cause of cancer-related deaths worldwide, with over 85% of the cases being of non-small cell lung cancer. Despite the recent advances, lung cancer remains undiagnosed until after the disease has advanced. The role of miRNAs in gene silencing is driven by RNA-induced silencing complex (RISC) consisting of Argonaute (AGO) protein. Understanding the miRNA-assisted gene regulation in lung cancer poses a prospect for an improved diagnostic and preventive measure towards the disease. This study explores miRNA interactions and their target genes in lung cancer, identifying four key miRNAs: miR-21-5p, miR-221-3p, miR-126-3p, and miR-34a-5p. These were shortlisted through their minimum free energy score, pattern conservation, functional, and network analysis. The AGO protein was retrieved, prepared for docking analysis with miRNA-mRNA duplexes, and docked using the HDOCK webserver. The docking results pointed towards the strong binding affinity of the miRNAs towards their targets and the AGO protein playing a crucial role as a driving force for gene expression. Furthermore, the miRNAs were established for their clinical relevance, particularly noting the association of high miR-21-5p expression with poor overall survival, suggesting potential avenues for further molecular investigation in lung cancer development.

The incidence of non-small cell lung cancer (NSCLC) has exhibited an elevated trend yearly, seriously threatening human health. However, its molecular mechanism is still unknown. The objective of this experiment was to investigate the expression and prognostic value of miR-766-3p in the tissues of NSCLC patients, as well as to provide possible targets for the healing of NSCLC. In this study, miR-766-3p and nuclear receptor subfamily 3 group C member 2 (NR3C2) were detected in tissues of NSCLC patients using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Survival analysis was estimated with Kaplan-Meier and Cox proportional hazards model. In vitro experiments included Cell Counting Kit-8 (CCK-8) viability assay, flow cytometry for apoptosis, Transwell assay for migration and invasion, and luciferase reporter assay for target genes. miR-766-3p levels were clearly elevated in tumor tissues, and high miR-766-3p levels were considered to be a poor prognostic factor. NR3C2 was clearly down-regulated in the serum of NSCLC patients. miR-766-3p overexpression stimulated the proliferation and enhanced metastatic spread of lung cancer cells, whereas down-regulation of NR3C2 reversed the effect of miR-766-3p on cellular activity. miR-766-3p promotes NSCLC development by inhibiting NR3C2 levels and is a potential biomarker. Furthermore, high levels of miR-766-3p are likely to predict poor prognosis in NSCLC.

The effector functions of CD8⁺ T cell significantly influence the immunosuppressive microenvironment in hepatocellular carcinoma (HCC), which is intricately associated with HCC prognosis. Nevertheless, a comprehensive investigation into the relationship between CD8⁺ T cell immune-related genes and HCC prognosis remains lacking. This study aimed to construct a prognostic model for HCC using CD8⁺ T cell immune-related genes to provide insights for clinical management and prognosis. A prognostic model was constructed by incorporating 16 CD8⁺ T cell-specific immune-related genes, yielding area under the curve (AUC) values of 0.821, 0.796, and 0.784 for the prediction of 1-year, 3-year, and 5-year survival, respectively, via receiver operating characteristic (ROC) curve analysis. The qRT-PCR results showed that the mRNA levels of PTMA, RAC1, HSPD1, HSP90AA1, and TANK were significantly higher in HCC cells compared to normal cells (p < 0.05). Further analysis focused on the TANK gene, which was significantly upregulated in HCC tissues (p < 0.05). The CCK-8 and wound healing assays revealed a significant decrease in both the cell proliferation rate and wound-healing rate in the TANK-deficient group compared with the control group (p < 0.05). These findings may offer new insights into the clinical treatment and prognostic evaluation of HCC.

The major oxidative adenine lesion, 7,8-dihydro-8-oxoadenine (oxoA), can readily undergo further oxidation to generate the highly genotoxic DNA interstrand cross-links (ICLs). Herein we report that the presence of single-strand breaks (SSBs), the major lesion formed at sites of oxidative stress, in the form of a nick or single-nucleotide gap in the phosphodiester backbone of duplex DNA significantly increases the cross-linking yield of oxoA with all canonical nucleotides (up to 67.5%) upon oxidation. The cross-linking reaction occurs between the purine/pyrimidine moiety of a nucleotide on the complementary strand of the duplex and the oxoA modification on the template strand, which was confirmed by the experiment involving the use of 2',3'-dideoxycytosine. Interestingly, the minor cross-linking products in intact DNA saw a more significant increase in reactivity relative to the major oxoA-G ICL. SSBs in the form of a gap or nick between the reacting nucleotide and thymine residue base paired to oxoA produced the most significant increase in yield.

Type 2 diabetes (T2D) is a complex multifactorial metabolic disorder characterized by progressive disease progression, involving varying degrees of insulin resistance and pancreatic islet dysfunction. Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme regulating folate metabolism, and its polymorphisms have been associated with T2D. However, the methylation pattern of the MTHFR gene has not been previously studied. This study aimed to assess the association between T2D and the methylation profile of the MTHFR gene promotor in a Moroccan population. A total of 107 patients with T2D and 100 healthy controls were included in the study. The methylation status of CpG sites in the MTHFR gene promoter was conducted by methylation-specific PCR (MS-PCR). Statistical analyses were performed using SPSS software (version 20). The promoter region of the MTHFR gene was predominantly hyper-methylated in patients with T2D compared to healthy controls (OR: 2.924; 95% CI: 1.285-6.650; p = 0.008). The hypermethylated profile was not influenced by environmental or metabolic factors examined in this study. These findings suggest that hypermethylation of CpG sites in the MTHFR gene promoter is associated with T2D in the Moroccan population, highlighting a potential epigenetic mechanism contributing to the disease.

The Epstein-Barr virus (EBV) infection status varies among BL subtypes. There are unresolved questions regarding the contribution of EBV, which is strongly associated with Burkitt lymphoma, to BL pathogenesis. Differences between EBV-positive and EBV-negative BL have been previously reported. A long-debated and studied topic is the differing origins of EBV-positive and EBV-negative BL cells. Studies have suggested that miRNAs, which are post-transcriptional elements involved in many pathways, play a role in this process. In our study, in silico analyses and a literature review were used to identify miRNAs potentially involved in lymphoma and B lymphocyte development pathways. Three miRNAs (miR-182, miR-320a, miR-144) targeting the BLIMP1 and XBP1 genes, which act as regulators in B lymphocyte development, and associated with lymphoma were identified. Paraffin-embedded tissue samples from 28 patients diagnosed with BL were included in the study. Real-Time PCR analysis of the BamHI-W and ApoB regions classified the samples into EBV-positive and EBV-negative groups. Expression analysis of the selected three miRNAs was performed using Real-Time PCR. Expression of miR-320a was observed in all samples, and a positive correlation was found between miR-320a expression and the viral load in the EBV-negative group. This study aimed to gain insights into the role of EBV in BL pathogenesis and has demonstrated the potential role of miR-320a. In conclusion, our study demonstrates that specific miRNAs are significantly associated with EBV in Burkitt lymphoma. These findings highlight the potential of targeting these miRNAs for therapeutic interventions and suggest further research into their mechanisms of action.