Exploring the therapeutic potential of NCX1 in hematological cancers; integration of molecular docking, bioinformatics approaches, and experimental validation.

Integrated Bioinformatic and Experimental Analysis Reveals the Molecular Mechanisms Underlying KDM1B/LSD2 Inhibition as a Therapeutic Strategy in Human Lung Adenocarcinoma.

Lung cancer remains a major global health challenge, and the oncogenic function of KDM1B (Lysine-specific Demethylase 1B) is still poorly characterized. This study employed integrated bioinformatics and experimental approaches to investigate KDM1B's function in lung cancer. Pan-cancer analysis using databases such as TIMER revealed notably elevated KDM1B mRNA expression in LUAD datasets, suggesting its potential as a diagnostic biomarker. A strong association was also found between increased KDM1B levels and immune cell infiltration in LUAD datasets. Protein interaction networks constructed using STRING and Cytoscape revealed close associations between KDM1B and key regulatory genes in NSCLC. KEGG enrichment analysis linked KDM1B to the mTOR signaling, which is critical for cell proliferation and survival. RT-PCR and western blotting for experimental validation showed KDM1B expression was significantly increased in A549 and NCI-H460 lung cancer cells. The deletion of KDM1B inhibits cell growth, induces G0/G1 phase cell cycle arrest, and promotes apoptosis in A54 cells. Moreover, cell proliferation was significantly inhibited by the KDM1B inhibitor, tranylcypromine, and induced G0/G1 phase cell cycle arrest, increased apoptosis, ROS, and glycolytic activity in A549 cells. Collectively, these findings highlight KDM1B as a valuable therapeutic target in lung adenocarcinoma and emphasize its key role in lung cancer development.

Multiomics, pharmacogenomic, and structural characterization of NCCRP1 as a candidate therapeutic target in ovarian cancer.

Bioinformatic characterization of SLC25A39 across cancers with validation in hepatocellular carcinoma

Functional enrichment analysis reveals that SLC25A39 is commonly associated with immune-related pathways and cell cycle-related pathways in the pan-cancer dataset.

Research progress on BTG2 in non-tumor diseases (Review)

This review systematically synthesizes advances in the pivotal, context-dependent roles of BTG2 in non-tumor pathologies, including fibrotic, neurological, cardiovascular, inflammatory, metabolic and other systemic diseases.

Multi-omics integration identifies HSPA4 as a therapeutic target and reveals DON-induced endoplasmic reticulum stress in bladder cancer

Background The therapeutic efficacy against bladder cancer is frequently constrained by chemotherapy resistance and high recurrence rates, underscoring the urgent need to identify novel therapeutic targets and develop effective intervention strategies. To address this challenge, this study employs an integrated approach combining bioinformatics analysis with experimental validation to systematically identify promising therapeutic targets and corresponding targeted drugs for bladder cancer. Methods An integrated analytical approach was employed to identify core genes associated with bladder cancer. This involved cross-validation of multiple transcriptomic datasets using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and summary data-based Mendelian randomization (SMR) analysis. Candidate drugs targeting these core genes were subsequently evaluated through a combination of database screening, molecular docking, and 100 ns molecular dynamics (MD) simulations to assess binding affinity. Finally, the expression of the targets, drug efficacy, and underlying mechanisms were experimentally validated in T24 and UMUC-3 cell lines using quantitative reverse transcription polymerase chain reaction (qRT-PCR), functional assays, and Western blot analysis. Results HSPA4 was consistently identified as a highly expressed core gene demonstrating a causal association with bladder cancer. The compound 6-Diazo-5-oxo-L-norleucine (DON) was predicted and subsequently validated to bind stably to HSPA4. In functional assays, DON significantly inhibited the proliferation, clonogenic formation, and migration capacity of bladder cancer cells. Mechanistic investigations revealed that DON downregulates HSPA4 expression, which induces IRE1α phosphorylation and upregulates the spliced form of XBP1 (XBP1s), thereby activating the endoplasmic reticulum stress (ERS) pathway. Furthermore, overexpression of HSPA4 partially reversed the antitumor effects of DON. Conclusions This study underscores the significance of HSPA4 as a potential therapeutic target in bladder cancer and demonstrates that DON exerts antitumor effects by targeting HSPA4 and activating the ERS pathway. These findings provide a novel candidate drug and a theoretical basis for targeted therapy against this malignancy.

Therapeutic Potential of Icariin in Breast Cancer: An Integrated Network Pharmacology and Molecular Simulations Approach

Breast cancer is a prevalent and aggressive tumor affecting women, known for its molecular diversity and treatment resistance. This study investigates the anticancer potential of Icariin (ICA), a flavonol glycoside derived from Herba epimedii, against breast cancer using network pharmacology and molecular simulation. Using the SwissTargetPrediction database and GeneCards, the researchers identified 98 common targets shared by ICA and breast cancer. Gene ontology (GO) and KEGG enrichment analyses highlighted the targets' roles in the regulation of apoptosis, inflammatory signaling, receptor tyrosine kinase activity, chemokine signaling, sphingolipid metabolism, and VEGF pathways. Molecular docking revealed ICA's strong binding affinity for key oncogenic proteins, with binding energies ranging from −12 to −7.5 kcal/mol, particularly to SER783, THR862, ASP863, LYS753, and ARG849. Molecular dynamics (MD) simulations demonstrated the structural stability of the ICA‐HER2 complex, which maintained strong hydrogen bonds and exhibited minimal conformational changes over a 1000 ns trajectory, with average RMSD values of 1.7 Å for the protein and 1.0 Å for the protein‐ligand complex. Furthermore, ICA exhibited favorable pharmacokinetic properties, including moderate solubility and negligible inhibition of cytochrome P450. These findings support the hypothesis that ICA may serve as a valuable natural compound for treating HER2‐driven breast cancer; it requires further experimental validation.