Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma, accounting for 75-80% of cases. Although Prohibitin 1 (PHB1) has been implicated in tumorigenesis, its role in KIRC remains unclear. This study aimed to investigate the expression, function, and underlying mechanisms of PHB1 in KIRC.

PHB1 expression and clinical relevance were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus database (GEO), and TIMER3.0 datasets. Single-cell RNA sequencing (scRNA-seq) data from 19 KIRC patients and normal kidney samples were used to assess cell-type-specific expression. Functional experiments, including CCK-8, EdU incorporation, colony formation, and Transwell assays, were performed to evaluate the effects of PHB1 on cell proliferation, migration, and invasion. A xenograft model was used to evaluate the effects of PHB1 in vivo. Western blotting and correlation analyses were conducted to assess the potential regulatory interplay between VHL, SKP2, PHB1, and p53.

PHB1 was significantly downregulated in KIRC tissues. Single-cell analysis showed reduced PHB1 expression in tumor-derived epithelial cells, fibroblasts, endothelial cells, and immune cells. Lower PHB1 levels were associated with poorer overall survival. PHB1 overexpression inhibited proliferation and migration, whereas knockdown promoted these effects. In vivo, PHB1 overexpression reduced tumor growth. Moreover, VHL knockout altered the protein levels of SKP2 and PHB1. Cellular manipulation of PHB1 moderately altered endogenous p53 protein expression. Based on TCGA data analysis, PHB1 expression showed a positive correlation with VHL and a negative correlation with SKP2.

Collectively, PHB1 acts as a potential tumor suppressor in KIRC. Its expression pattern is associated with the VHL-SKP2 signaling axis, and the tumor-suppressive effects of PHB1 may be partially associated with the modulation of p53 expression. These findings suggest that PHB1 has the potential to serve as a reliable biomarker and therapeutic candidate for KIRC treatment.

G protein-coupled receptor 19 (GPR19) is an orphan G protein-coupled receptor with emerging relevance in cancer; however, its role in breast cancer remains poorly understood. Given the high frequency of tumor protein p53 (TP53) alterations in aggressive breast cancer, particularly triple-negative breast cancer (TNBC), we investigated the clinical significance, biological function, and molecular mechanism of GPR19 in TP53-mutant breast cancer.

Public datasets (Gene Expression Omnibus and The Cancer Genome Atlas) were analyzed to assess GPR19 expression in relation to TP53 status, molecular subtype, and prognosis. Expression was validated in breast cancer cell lines, paired clinical tissues, and tissue microarrays by quantitative PCR, Western blotting, immunofluorescence, and immunohistochemistry. Stable GPR19 knockdown models in MDA-MB-231 and BT-549 cells were used to evaluate proliferation, cell cycle distribution, and apoptosis. RNA sequencing, rescue experiments with the extracellular signal-regulated kinase (ERK) activator Ro 67-7476, and a nude mouse xenograft model were employed to investigate the underlying mechanism.

GPR19 was significantly upregulated in TP53-mutant breast cancer, primary tumors, and especially TNBC, and its high expression was associated with poor survival. Functionally, GPR19 depletion markedly suppressed cell proliferation, colony formation, and DNA synthesis, while inducing G2/M arrest and apoptosis in TP53-mutant breast cancer cells. Mechanistically, GPR19 knockdown reduced ERK phosphorylation and downregulated forkhead box protein M1 (FOXM1) and its downstream G2/M regulators cyclin B1 (CCNB1) and polo-like kinase 1 (PLK1), whereas total ERK levels remained largely unchanged. Pharmacological activation of ERK partially restored FOXM1 expression, alleviated cell cycle disturbance and apoptosis, and reversed the growth-inhibitory effects of GPR19 depletion. In vivo, GPR19 knockdown suppressed xenograft growth, reduced Ki-67 staining, increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positivity, and inhibited the ERK-FOXM1-CCNB1/PLK1 signaling cascade, all of which were partially rescued by ERK activation.

GPR19 functions as a novel oncogenic driver and clinically relevant biomarker in breast cancer, particularly in TP53-mutant and TNBC subsets. By activating the ERK-FOXM1 axis, GPR19 sustains cell cycle progression and suppresses apoptosis, highlighting this pathway as a potential therapeutic vulnerability in aggressive breast cancer.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a major cause of cancer-related mortality. Despite advances in targeted therapies, tumor heterogeneity and acquired resistance frequently undermine clinical outcomes. This study aimed to identify novel oncogenic drivers and underlying mechanisms in LUAD.

We examined cellular retinoic acid-binding protein 2 (CRABP2) expression in human LUAD specimens and evaluated its functional role through in vitro assays (cell proliferation, migration, invasion, and apoptosis) and in vivo xenograft tumor growth. Mechanistic exploration involved RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and immunoblotting for the nuclear factor kappa B (NF-κB) signaling components, along with rescue experiments to dissect the pathway dependency.

CRABP2 was identified as a candidate oncogene in LUAD. Functional assays confirmed that CRABP2 promoted proliferation, migration, and invasion, suppressed apoptosis, and accelerated xenograft tumor growth. Mechanistically, CRABP2 potentiated retinoic acid (RA) signaling and activated the NF-κB pathway, as evidenced by enhanced inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) phosphorylation, subsequent NF-κB inhibitor alpha (IκBα) phosphorylation, and nuclear translocation of total and phosphorylated p65. Rescue experiments revealed that CRABP2‑induced NF-κB activation is RA-dependent and that this activation mediates the oncogenic effects of CRABP2.

Our findings establish a CRABP2/RA/NF‑κB axis that drives LUAD progression, highlighting this pathway as a potential therapeutic target for intervention in LUAD.

While mitochondrial dysfunction and immune cell dysregulation have been established as important contributors to the pathogenesis of osteosarcoma (OS), the prognostic value of mitochondria-related genes (MRGs) and immune-related genes (IRGs) in OS remains poorly understood.

Data were obtained from public databases. Differentially expressed genes (DEGs) and key module genes were identified viadifferential expression analysis and weighted gene co-expression network analysis, respectively. Candidate genes of interest were identified by intersecting key module genes, DEGs, MRGs, and IRGs. Then, candidate genes were screened using regression analysis and proportional hazards assumption testing to identify prognostic genes. A risk model was then constructed in the TARGET-OS dataset and validated in GSE16091. Independent prognostic, immune infiltration, and gene expression analyses were conducted. In addition, single-cell analysis was performed to identify key cell populations, and pseudotime analysis as well as cell communication network construction were carried out. Finally, the expression patterns of selected prognostic genes were additionally validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the functional role of protein kinase Cα (PRKCA) in osteosarcoma cell proliferation, migration, and invasion was evaluated in vitro.

Glutathione S-transferase Pi-1 (GSTP1), catalase (CAT), TNFSF10, and PRKCA were identified as mitochondria- and immunity-related prognostic genes in OS and were used to construct a risk model. The risk model was able to effectively predict the survival of patients with OS. A nomogram based on the identified prognostic genes additionally exhibited excellent performance when predicting OS patient survival. Significant differences in the abundance of 14 immune cell types and 8 immune checkpoint molecules were noted between the high-risk and low-risk groups. Single-cell analyses were then conducted to annotate 10 cell types, and M1 macrophages were identified as a potentially relevant cell population in the OS microenvironment. During M1 macrophage differentiation, initial reductions in CAT and PRKCA expression were noted, followed by subsequent increases and final decreases. In contrast, the expression of GSTP1 and TNFSF10 in these cells first rose and then declined. Furthermore, PRKCA was selected for further in vitro analyses, which revealed that it can enhance the invasion, migration, and proliferation of OS cells.

This study identified GSTP1, CAT, TNFSF10, and PRKCA as prognostic genes associated with mitochondrial and immune function in OS, with in vitro evidence providing direct support for the potential functional role of PRKCA in OS progression. These findings highlight a new avenue for predicting clinical prognosis in OS and may provide a basis for future studies of putative therapeutic targets.

Methyltransferase-like 9 (METTL9) has been implicated in tumor progression, yet its clinical significance, functional roles, and immunoregulatory functions in lung adenocarcinoma (LUAD) remain unclear. This study aimed to integrate multi-omics datasets and experimental evidence to systematically evaluate the expression profile, prognostic value, molecular mechanisms, and tumor microenvironment (TME)-related functions of METTL9 in LUAD.

Transcriptome and clinical data for LUAD and METTL9 protein expression were obtained from public databases. Survival analysis was performed using Kaplan-Meier analysis and Cox proportional hazards models. METTL9-related differentially expressed genes (DEGs) were screened, followed by functional annotation and pathway enrichment analysis. A protein-protein interaction (PPI) network associated with METTL9 was constructed using STRING. METTL9 gene mutations and promoter methylation levels were analyzed via cBioPortal and UALCAN. Immune infiltration was evaluated through gene set variation analysis (GSVA) and the TIMER platform. The role of METTL9 depletion in regulating transforming growth factor-β (TGF-β)/Smad signaling, epithelial-mesenchymal transition (EMT), as well as the behavior of A549 and H1975 cells was investigated.

METTL9 was markedly elevated in LUAD, which was confirmed in external datasets and immunohistochemistry. Increased METTL9 expression showed a strong association with advanced TNM stage, unfavorable clinicopathological parameters, and poor survival outcomes in univariate analysis. Receiver operating characteristic (ROC) analysis indicated that METTL9 showed moderate diagnostic utility for LUAD, with an Area Under the Curve (AUC) of 0.704 (95% Confidence Interval [CI]: 0.650-0.758) in the The Cancer Genome Atlas (TCGA) dataset and 0.815 (95% CI: 0.758-0.872) in the GSE31210 dataset. Moreover, high METTL9 expression was significantly correlated with poor survival outcomes (Hazard Ratio [HR] = 1.349, 95% CI: 1.010-1.802, p = 0.043). METTL9 interacted with multiple oncogenic proteins in the PPI network and showed significant correlations with cuproptosis-related genes. Immune infiltration analysis further demonstrated that METTL9 expression showed significantly associated with immune cell infiltration and the tumor immune microenvironment in LUAD. METTL9 knockdown suppressed LUAD cell proliferation, migration, invasion, and EMT, while promoting apoptosis and reducing the expression of B-cell lymphoma 2 (Bcl-2), phosphorylated Smad2 (p-smad2), and phosphorylated Smad3 (p-smad3).

METTL9 is upregulated in LUAD and correlates with an unfavorable prognosis. Our results indicate that METTL9 may contribute to LUAD progression and EMT, potentially in relation to the TGF-β/Smad signaling pathway.

Intracranial aspergilloma is a rare fungal infection of the central nervous system, predominantly affecting immunocompromised individuals. However, cases in immunocompetent hosts are increasingly reported, often mimicking meningiomas due to similar radiological features, leading to diagnostic delays and poor outcomes.

We present two cases of isolated intracranial aspergilloma in immunocompetent patients. The first case involved a 55-year-old female with a right parietal scalp swelling mimicking a convexity meningioma, confirmed as aspergilloma on histopathology following surgical excision. The second case was a 63-year-old male with symptoms of raised intracranial pressure and a right planum sphenoidale lesion mimicking skull base meningioma, also diagnosed postoperatively as invasive aspergillosis. Both patients underwent surgical resection and voriconazole therapy, with favorable short-term outcomes. These cases highlight the diagnostic challenges posed by overlapping imaging characteristics of aspergilloma and meningioma.

A high index of suspicion, even in immunocompetent patients, is essential for timely histopathological confirmation and antifungal treatment to mitigate morbidity and mortality. Adding aspergilloma to the differential diagnosis of meningioma-like lesions on radiology may improve outcomes.

Glioblastoma (GBM) frequently develops resistance to temozolomide (TMZ), limiting the effectiveness of standard therapy. Histone deacetylase (HDAC) inhibitors have emerged as potential chemosensitizers; however, the comparative performance of these inhibitors and the associated mechanistic impact remain incompletely characterized.

In vitro, this study systematically evaluated the effects of the Class I-selective HDAC inhibitors Entinostat and Tucidinostat, and the pan-HDAC inhibitor Vorinostat on TMZ sensitivity in multiple GBM cell lines (U87, U251, LN229). Additionally, this study assessed cell viability, morphology, and the expression of selected markers glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), class III β-tubulin (TUBB3), and synapsin I (SYN1). In vivo, the therapeutic efficacy of Entinostat combined with TMZ was evaluated in a U87 xenograft mouse model by measuring tumor growth, and the expression of GFAP and TUBB3 was examined in tumor tissues. Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9 (CRISPR-Cas9)-mediated knockout of HDAC1/2/3 was used to test the dependence of these effects on canonical Class I HDACs.

Entinostat and Tucidinostat significantly enhanced TMZ-induced cytotoxicity across all cell lines, demonstrating greater TMZ-sensitizing activity than Vorinostat under the conditions tested. Treatment was associated with altered cell morphology and changes in marker expression, including reduced GFAP and increased MAP2 and TUBB3. In the U87 xenograft model, Entinostat combined with TMZ significantly suppressed tumor growth and was associated with decreased GFAP and increased TUBB3 expression. Importantly, both TMZ sensitization and the associated morphological and marker changes persisted in HDAC1/2/3-knockout cells, suggesting that the effects are not fully explained by HDAC1/2/3 depletion. These effects were consistent across multiple cell lines and in xenograft tumors.

Entinostat and Tucidinostat enhance TMZ sensitivity in GBM models and are associated with specific markers and morphological changes that persist despite HDAC1/2/3 knockout. These findings support further evaluation of Entinostat and Tucidinostat as TMZ-sensitizing agents in GBM models and highlight associated phenotypic and molecular changes that warrant further mechanistic validation.

Cancer neuroscience has emerged as a field that explores the bidirectional interactions between tumors and the nervous system. From this perspective, we review the pharmacological and neurobiological effects of kinase inhibitors, which are widely used as anticancer therapeutics. Certain kinase inhibitors not only exert potent antitumor activity but also modulate neural function as a consequence of kinase inhibition. Representative examples include small molecules and therapeutic antibodies targeting the tropomyosin receptor kinase (Trk), rearranged during transfection (RET), vascular endothelial growth factor/ vascular endothelial growth factor receptor (VEGF/VEGFR), epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) signaling pathways. These agents influence the nervous system through molecular mechanisms, examples of which include TrkA-mediated pain perception and growth differentiation factor 15/RET signaling-dependent appetite regulation. Elucidating these mechanistic intersections between oncogenic and neural signaling can broaden our understanding of tumor-nerve crosstalk.

A common cause of multidrug-resistant (MDR) cancer is imbalanced redox signaling, which reduces the effectiveness of chemotherapy and promotes regrowth of cancer cells. Amplification of thioredoxin reductase (TrxR) and activation of the Keap1-Nrf2-FOXO3 pathway may contribute to enhanced drug efflux, strengthens antioxidant defenses, and resistance to oxidative stress-induced apoptosis in certain tumors. Redox-based drug repurposing offers a promising strategy to overcome MDR by targeting these shortcomings. Repurposing drugs including metformin, auranofin, brusatol, and natural polyphenols increase reactive oxygen species (ROS) and make MDR cells more sensitive to chemotherapy via modulation and inhibiting Nrf2 or TrxR. Nanotechnology advancements and combination of repurposed drugs with anticancer drugs, ferroptosis inducers may improve tumor selectivity while lowering systemic toxicity. Preclinical experiments show effectiveness by suppressing antioxidant pathways, inhibiting efflux pump function, and delivering drugs in a redox-responsive manner. Next-generation tumor-selective delivery systems, adaptive clinical trial designs, and biomarker-driven patient classification based on TrxR expression or Keap1/Nrf2 mutations are the main areas of focus. Translation into clinical practice could be accelerated by combining specific redox profiling, nanocarrier technologies, and pharmacokinetics. For MDR cancer, redox-targeted drug repurposing is an effective, precision-based strategy for recovering chemosensitivity and enhancing treatment outcomes.

Bladder cancer is a long-standing clinical issue, with frequent recurrence and continuously disappointing results in patients, so that therapeutic development is primarily reliant on delineating the original molecular defects. Increasing interest has turned to the Kinesin Superfamily Proteins (KIFs), basic molecular motors that move along microtubule rails, and are now emerging as important key oncogenic derivers in bladder cancer pathogenesis. This review synthesizes available evidence indicating that several KIFs, specifically KIF4A, KIF14, KIF20A, and KIFC1, function as key oncogenic regulators and represent important prognostic biomarkers and therapeutic targets in bladder cancer. When KIF expression or activity is disrupted, it provides mechanical and signaling support for all the cancer hallmarks, facilitating cellular proliferation, invasion, metastasis, and resistance to highly effective cell death. Its oncogenic activity is generally facilitated by the activation of principal signaling pathways. A remarkable proportion of certain KIF isoforms are commonly overexpressed in cancer, and the scale of such overexpression increases with the severity of adverse clinical predictors, such as increasing disease stage, and patient survival worsens. This nuanced molecular image renders KIFs so highly promising targets for therapeutic intervention and prognostic stratification, and initial exploration of kinesin inhibitors is encouraging to abate chemoresistance, aside from optimizing the efficacy of current immunotherapies. Uncovering modalities that exploit the aggressive bladder cancer cell dependence on KIF motor activity is a highly promising path to clinical application.