Nucleosides, Nucleotides & Nucleic Acids最新文献

Lung squamous cell carcinoma (LUSC), a prevalent non-small cell lung cancer subtype, demonstrates marked heterogeneity and unpredictable prognosis. This study established a prognostic model using STING pathway-related genes to stratify LUSC patients and guide immunotherapy. Through weighted gene co-expression network analysis of TCGA-LUSC data, we identified the MEbrown module containing 13 STING-associated key genes (including CD47 and CLDN5) to develop the STING Pathway Death-Related Signature (SPDRS). LASSO regression refined the model, which effectively stratified patients into distinct high- and low-risk groups with significant survival differences. High-risk patients exhibited enhanced immune infiltration, particularly T cells CD4 memory resting and M2 macrophages, along with elevated immune checkpoint expression and stromal scores. Functional analyses revealed enrichment in immune-related pathways and tumor microenvironment regulation. Drug sensitivity predictions identified potential therapeutic agents targeting SPDRS components. A nomogram integrating SPDRS with clinical factors demonstrated strong prognostic accuracy. This work provides a novel STING pathway-based stratification system that elucidates tumor microenvironment heterogeneity and informs personalized treatment strategies. The findings highlight SPDRS as both a prognostic biomarker and therapeutic response predictor, advancing precision immunotherapy in LUSC management.

Examination of structures of DNA duplexes (A-, B-, and Z-DNA) showed a positive correlation between the pseudorotational phase angle P and the torsion angle δ_H (H4'-C4'-C3'-H3'). Such a P - δ_H plot reflects the structural features of the three types of DNA duplexes. Since the δ_H torsion angle can be measured by nuclear magnetic resonance, the linear correlation between P and δ_H provides a useful method for predicting the sugar pucker of nucleosides and nucleic acids.

Cancer cells often evade immune detection and destruction by inducing immune suppression genes, which include CTLA-4, TGF-β, and PD-L1, that inhibit immune responses and promote tumour progression. Recent studies have highlighted the significance of non-coding RNAs, particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in regulating these immune suppression pathways. miRNAs, short RNA molecules that target mRNA of immune genes at the post-transcription level and influence gene expression. Similarly, lncRNAs, which act as molecular scaffolds, sponges, or regulators of gene expression, are involved in modulating immune responses by interacting with miRNAs or directly binding to immune-related genes. This review explores the complex interplay between miRNAs, lncRNAs, and immune suppression genes, detailing how these non-coding RNAs contribute to immune evasion in cancer. Furthermore, the therapeutic potential of targeting these regulatory networks is examined, highlighting current strategies and challenges in using miRNA and lncRNA modulators to enhance anti-tumour immunity. Understanding these intricate regulatory networks offers new insights into the mechanisms of immune suppression in cancer and opens avenues for developing novel therapeutic interventions to restore immune surveillance and improve the efficacy of cancer immunotherapies.

Contemporary cancer treatments encompass diverse strategies like surgery, chemotherapy, radiation, immunotherapy, and targeted therapies, aiming for effective cancer cell control with minimal impact on healthy tissues. Aptamers are short nucleotide sequences typically containing 25-80 bases and can attach to specific target molecules as effectively as monoclonal antibodies. While the FDA has yet to approve any aptamers for oncology applications, a few, such as Pegaptanib (Macugen), have been approved for ophthalmologic conditions like age-related macular degeneration. Pegaptanib and Izervay are the approved aptamers against age-related macular degeneration (AMD) that target vascular endothelial growth factor (VEGF) and block complement component protein C5, respectively. A new type of highly sensitive and specific biosensor has recently been created to detect leukaemia cancer cells. Aptamosomes, encapsulating drugs like doxorubicin, effectively reduce tumour size and are highly advantageous over targeted drug delivery. Many aptamers have been generated against ERα, Epithelial cell adhesion molecule, EGFR, B subunit of platelet-derived growth factor, Vimentin, Osteopontin, Type II membrane protein PSMA, MUC-1, AXL receptor tyrosine kinase, CD28 agonistic aptamer, as well as for the B7-CD28 interaction, etc. This review suggests the pros and cons of aptamer usage and its advantages over antibody treatment. It also outlines the roles of aptamers and connects their modes of action with specific cancer types. The content is highly detailed, providing a comprehensive understanding of aptamer therapy and its applications.

Axitinib is an oral medication classified as a second-generation tyrosine kinase inhibitor. It serves as a primary treatment for metastatic renal cell carcinoma (RCC) due to its strong affinity for DNA, which leads to the disruption of the double helix structure. This disruption ultimately halts the cell cycle and induces senescence and mitotic catastrophe in RCC cells. Consequently, investigating the mechanism by which Axitinib binds to DNA is essential for comprehending its pharmacodynamic properties and for the advancement of more effective DNA-binding therapeutics. The present study aimed to examine the interaction between Axitinib and DNA through various analytical techniques, including UV-Vis spectroscopy, thermal denaturation assays, electrochemical methods, and fluorescence emission spectroscopy. According to the electrochemical studies, the binding constant (K_b) for Axitinib was calculated to be (5.13 ± 0.28) × 10⁴, suggesting the potential for groove binding. This finding was further supported by in-silico analyses, where molecular docking and molecular dynamics simulations indicated that the drug selectively binds to the DNA minor groove through partial intercalation, forming new hydrogen bonds with its functional groups while separating the guanine and cytosine base pairs.

Understanding the interaction of therapeutic drugs with DNA is crucial for designing highly selective DNA-targeted medicines that could overcome the current therapeutic limitations. In this endeavour, the DNA binding behaviour of arbutin (ATN) was explored using multi-spectroscopic, electrochemical and computational studies. The UV-Vis spectral studies authenticated the complexation of ATN with CT-DNA and exposed ATN as a moderately strong DNA binder with a binding constant of 8.029 × 10³ M^-1. The findings of fluorescence spectral studies not only revealed the spontaneous ground state complex formation between ATN and CT-DNA, but also emphasised the role of hydrogen bonding and Van der Waals interactions in stabilising the ATN/CT-DNA complex. Since the competitive dye displacement assay strongly excluded the plausibility of classical intercalation and conventional groove binding mode of ATN, viscosity studies provided clues regarding the external binding mode of ATN. The appreciable enhancement resulted in the fluorescence emission of the ATN/CT-DNA complex upon increasing NaCl concentration, which certified ATN as an external binder. The CD spectral results exposed the ATN-induced moderate conformational alterations in CT-DNA. Remarkably, the voltammetric titration results labelled the glucopyranoside moiety of ATN as a DNA binding unit with a formation constant of 2.57 × 10⁴ M^-1 rather than the hydroquinone moiety of ATN. Molecular docking and metadynamics simulation outcomes served as pictorial evidence of experimental results. They revealed the predominant contribution of hydrogen bonding interactions in stabilising ATN/DNA complexation.

Background: Esophageal cancer (EC) is among the deadliest malignancies in humans, with various miRNAs shown to regulate its progression by targeting distinct genes. miR-508-5p was identified as being linked to the malignant behavior of various tumors. Nevertheless, the precise role and mechanism of miR-508-5p in esophageal cancer (EC) remain ambiguous.

Objective: This investigation focuses on the role and mechanism of the miR-508-5p/TSGA10 axis in the progression of EC.

Methods: The expression of miR-508-5p and TSGA10 in EC cell lines was evaluated using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Cell transfection techniques were used to knock down miR-508-5p and observe its effects on cell proliferation, migration, invasion, and apoptosis. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship of miR-508-5p with TSGA10. Co-culture studies were undertaken to examine the regulatory effect of the miR-508-5p/TSGA10 axis on the polarization state of tumor-associated macrophages (TAMs) and the malignant behavior of EC cells.

Results: The expression of miR-508-5p was significantly elevated in EC cells. Knocking down miR-508-5p curbed cell proliferation, migration, and invasion while promoting apoptosis. TSGA10 was validated as a primary target gene of miR-508-5p. miR-508-5p knockdown could inhibit the M2 polarization of TAMs by upregulating TSGA10, thereby suppressing the tumorigenic behavior of EC cells.

Conclusion: miR-508-5p promotes the M2 polarization of TAMs and enhances the malignant behavior of EC cells by inhibiting TSGA10.

Bacteriophage-based gene delivery systems are emerging as a promising alternative to traditional viral and non-viral vectors for targeted gene therapy in breast cancer. Their unique structural adaptability, low immunogenicity, and cost-effective production make them ideal candidates for precision medicine applications. Unlike conventional gene delivery platforms, bioengineered bacteriophages can be functionalized with tumor-specific ligands, modified for PEGylation to enhance circulation stability, and integrated with CRISPR/Cas9 gene-editing systems for precise genomic modifications. Additionally, bacteriophage vectors can be utilized in combination therapy, amplifying the effectiveness of chemotherapy and immunotherapy in breast cancer treatment. This mini-review discusses the bioengineering strategies used to enhance bacteriophage-based gene delivery, including surface modifications for tumor targeting, ligand-receptor binding for cellular uptake, and controlled genetic cargo release. We further examine in vitro and in vivo studies that demonstrate the potential of bacteriophage vectors in tumor suppression, gene expression efficiency, and immunomodulation. Furthermore, we explore the challenges and future directions of integrating bacteriophage-mediated gene therapy into clinical applications, addressing key issues such as systemic circulation half-life, off-target effects, and immune system interactions.

LncRNAs serve as crucial regulators in the survival and proliferation of tumors. This study is dedicated to exploring the functional significance of lncRNA PGM5-AS1 in breast cancer (BRCA). First, the expression level of PGM5-AS1 in BRCA patients and its diagnostic ability for BRCA were analyzed by RT-qPCR and Receiver Operating Characteristic curve. Subsequently, LnCAR database was used to preliminarily explore the relationship between PGM5-AS1 and prognosis. Moreover, we investigated the effects PGM5-AS1 on proliferation, apoptosis, and migration of BRCA cells by MTT assay, flow cytometry, and Transwell assay. More importantly, the regulation effect of PGM5-AS1 on the downstream target miR-182-5p was verified by dual luciferase reporting experiment, and the role of miR-182-5p was further explored in vitro experiments. PGM5-AS1 is significantly decreased in both BRCA patients and BRCA cell lines. In the diagnosis of BRCA, the sensitivity and specificity of PGM5-AS1 were 81.5% and 78.5%. Furthermore, lower levels of PGM5-AS1 are associated with a poor prognosis for affected patients. In vitro studies demonstrate that the upregulation of PGM5-AS1 confers a protective effect against BRCA, markedly inhibiting the viability and migratory capacity of tumor cells. More importantly, overexpression of PGM5-AS1 inhibited the high expression of miR-182-5p in tumor cells. In fact, inhibition of miR-182-5p is detrimental to the proliferation and migration of BRCA cells in vitro. lncRNA PGM5-AS1 has potential as a diagnostic marker for BRCA and acts as an inhibitor in BRCA. It inhibits tumor proliferation and metastasis by targeting miR-182-5p.

Objective: This study aimed to explore the diagnostic and prognostic value of miR-378c in hepatocellular carcinoma (HCC) patients.

Methods: This study included 97 HCC patients, 84 cirrhosis patients and 80 healthy volunteers. Serum miR-378c of all subjects and HCC cell lines was detected by qRT-PCR, and ROC curves were plotted to assess the clinical diagnostic value of miR-378c for HCC. The prognostic performance of miR-378c in HCC was assessed using the Kaplan-Meyer method and COX regression analysis. CCK-8 test for proliferation of HCC cell lines. The migration and invasion of HCC cell lines were measured by Transwell assay. Bioinformatics analysis was employed to analyze the possible target genes of miR-378c.

Results: Serum miR-378c were remarkably lower in HCC patients than in cirrhosis patients and healthy controls (p < 0.001). ROC curves indicated that serum miR-378c could effectively distinguish HCC patients from healthy controls and cirrhotic patients. Among HCC patients, those with high miR-378c expression had higher cumulative survival (p = 0.001), and COX analysis identified miR-378c as an independent prognostic biomarker for HCC. Overexpression of miR-378c significantly inhibited the proliferation, migration and invasion of MHCC97H and HepG2 cells (p < 0.01). Bioinformatics analysis of miR-378c target genes revealed that miR-378c target genes were enriched in tumor-associated pathways.

Conclusion: Serum miR-378c expression is decreased in HCC patients and strongly connected with poor prognosis. As a potential diagnostic and prognostic biomarker for HCC patients, it may provide new insights into the diagnosis and prognosis of HCC.