Although autophagy-related gene 7 (ATG7) acts as an E1-like activating enzyme and is essential for autophagy, it frequently performs broader roles involved in the modulation of diverse signaling pathways that affect cell proliferation, survival, migration and transformation. ATG7 is often downregulated in various cancers. However, the role of ATG7 in fibroblasts in regulating breast carcinoma remains poorly understood. Herein, we revealed that aberrantly low expression of ATG7 in breast stroma is clinically relevant to breast cancer progression. Loss of ATG7 expression results in fibroblasts acquiring the hallmarks of cancer-associated fibroblasts (CAFs), which finally promote the proliferation, metastasis of breast cancer in vivo and vitro. Detailed regulatory mechanisms showed that ATG7-deficient fibroblasts secrete a new miRNA (miR-6803b) and are then transported into breast cancer cells by exosomes. In breast cancer, miR-6803b targets the SCARB1 gene to inhibit its expression and then promote cancer cell metastasis, resulting in cancer progression. Thus, our results indicate that ATG7 expression in fibroblasts plays a vital role in regulating breast cancer tumorigenesis and progression by modifying stromal-epithelial crosstalk and remodeling the tumor microenvironment (TME). These results suggest that ATG7 can function as a tumor suppressor and represent a new candidate for prognosis and targeted therapy.

Cervical cancer remains the second leading cause of female cancer mortality worldwide, with metastasis representing a critical therapeutic challenge. This study systematically reveals the key role of SERPINH1 (Serpin Family H Member 1) as a hub regulator of malignant progression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Through analysis of TCGA-CESC datasets, we identified that high SERPINH1 expression is significantly correlated with poor prognosis and contributes to tumor progression by promoting cell proliferation, invasion, and metastatic phenotypes. In vitro experiments validated these findings, demonstrating that SERPINH1 overexpression markedly enhanced the proliferation, invasion, and metastasis of cervical cancer cells, whereas its knockdown substantially inhibited these processes. Furthermore, based on the SERPINH1-related differentially expressed genes, a prognostic risk model was constructed, successfully identifying PLOD1, ITGA5, and ESM1 as core collaborative genes affecting patient prognosis. Overall, our findings underscore the multiple functions of SERPINH1 as a hub for cervical cancer metastasis regulation, suggesting its potential as a promising biomarker for tailoring strategies in metastasis patients of CESC.

Glioblastoma is the most common primary malignant brain tumor. It is aimed to elucidate the role of ROCK in the regulation of PI3K signaling inhibited by PTEN and to evaluate the effects of ROCK inhibitors Thiazovivin and GSK 429286 on glioblastoma as a new therapeutic strategy. U87 MG and L929 cell lines were used to research the cytotoxic effect of ROCK inhibitors Thiazovivin and GSK 429286. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and xCELLigence real-time cell analyzer were used to determine its effect on cell viability. To assess the impact of ROCK inhibitors on PTEN protein levels, PTEN expression in cell lysates was quantitatively determined in vitro using the PTEN ELISA Kit. Total protein concentration was measured using the BCA protein assay kit, p-Akt and PTEN protein level was determined by the western blot method. Showed that GSK 429286 and Thiazovivin significantly reduced U87 MG cell viability even at low concentrations. When IC₅₀ values were examined, it was understood that THV (IC₅₀: 11.02 µM) showed a more potent cytotoxic effect at lower concentrations compared to GSK 429286 (IC₅₀: 89.58 µM). At 50 µM, Thiazovivin and GSK 429286 concentration caused a significant increase in PTEN activity compared to the control and Temozolomide groups, even at low concentrations. THV 50 μM significantly increased PTEN expression compared to control (p < 0.05). GSK 50 μM, THV 1 μM, and THV 10 μM groups showed significantly reduced p-Akt expression (p < 0.05). Considering the effects on healthy cells, Thiazovivin being more effective at low doses suggests it may be a more selective agent. Our findings indicate that ROCK inhibitors may have cytotoxic effects on glioblastoma cells by affecting cell death mechanisms via a PTEN-associated reduction in PI3K/AKT signaling.

Methyltransferase-like protein 7A (METTL7A), an m6A methyltransferase, is closely associated with various cancers, but its role in acute myeloid leukemia (AML) remains unclear.

This study employed bioinformatics analysis using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Furthermore, METTL7A expression levels in AML samples were validated using qRT-PCR.

Analyses of TCGA, GTEx, and a single-center cohort all revealed significantly higher METTL7A expression in AML patients compared to controls. High METTL7A expression correlated with poor prognosis and pathological features. ROC curve analysis confirmed its diagnostic value, while multivariate analysis identified METTL7A as an independent prognostic risk factor, leading to the development of a prognostic nomogram. KEGG and GSEA analyses indicated METTL7A's involvement in immune regulation, which was further supported by immune infiltration analysis showing its association with immune cell infiltration.

High METTL7A expression is associated with poor prognosis in AML and may be a potential diagnostic and prognostic biomarker.

To analyze the clinicopathological features, immunological characteristics, and prognostic value of APOBEC3C in gliomas, and to verify the specific mechanism by which it mediates the malignant progression of gliomas.

mRNA-seq data from 693 glioma patients in the CGGA database and 697 glioma patients in the TCGA were analyzed, respectively. In addition, single-cell sequencing data were obtained from the CGGA database. Bioinformatics methods were applied to reveal the possible mechanisms of APOBEC3C-mediated malignant progression of gliomas. Moreover, western blot, transwell, and cell-scratch assays were used to explore the potential mechanisms of APOBEC3C-mediated glioma invasion and migration.

APOBEC3C was enriched in malignant glioma subtypes and was a potential biomarker for mesenchymal subtypes in glioma patients. It was closely associated with glioma inflammation and immunity. Additionally, APOBEC3C is a potential independent prognostic factor for glioma, and inhibition of APOBEC3C expression can suppress the EMT process in glioma cells through the NF-κB signaling pathway.

APOBEC3C is a potential biomarker for glioma patients. It is closely related to the clinicopathology of glioma and may be a potential immunotherapy target for glioma patients.

Lactate-driven metabolic reprogramming and histone lactylation play pivotal roles in bladder cancer (BLCA) progression, yet their underlying mechanisms and regulatory genes remain poorly understood.

Using transcriptomic data from The Cancer Genome Atlas (TCGA), we identified lactylation-associated genes and constructed a prognostic signature. Comprehensive bioinformatics analyses were conducted to assess immune infiltration, tumor microenvironment characteristics, and the lactylation landscape at the single-cell level. Furthermore, we performed in vitro experiments to evaluate the biological functions of key lactylation-related genes in BLCA cells.

Six lactylation-related hub genes were identified, among which FASN and RUNX2 were significantly upregulated in BLCA and associated with poor prognosis. Single-cell analyses revealed elevated lactylation signatures in tumor epithelial and immune cells. Knockdown of FASN or RUNX2 in BLCA cell lines significantly suppressed cell proliferation, induced apoptosis, and reduced intracellular lactate levels. Correspondingly, global protein lactylation was diminished, with dominant modification signals observed around 40 kDa, indicating a potential set of non-histone proteins as key functional targets.

Our study highlights a metabolic-enzymatic axis wherein FASN and RUNX2 regulate lactate-driven protein lactylation in BLCA. These findings provide new insights into the non-histone functions of lactylation and suggest potential therapeutic targets at the intersection of metabolism and tumor immunity.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer that typically affects women ages 20 to 50, presenting as an asymptomatic neck mass. Treatment with total or partial thyroidectomy shows an excellent prognosis. However, investigation of non-invasive therapeutic options with minimal adverse effects is ongoing. This study seeks to investigate the K1 cell line, which consists of PTC cells obtained from metastatic tumors of well-differentiated PTC.

Our investigation focuses on a cannabinoid-based product (named BRF1-A) and its potential anti-cancer effects through modulation of gene expression. We investigated its effects on gene expression of p53, c-Myc, and BCL-2 in K1 papillary thyroid cancer cells.

BRF1A was co-cultured with K1 cell line (1 × 10⁶ cells/ml) and incubated at 37°C under 5% CO₂ for 24 and 48 hours. After the culture time points, the cells were harvested, and cell viability was determined via trypan blue exclusion assay. Using qRT-PCR, we determined the effect on the gene expression of TP53, c-Myc, and BCL-2.

Results show that the BRF1A decreased the viability of K1 PTC cells in a dose and time-dependent manner. Within 24 hours, the cannabinoid- containing product increased the gene expression of TP53 and decreased the gene expression of BCL-2 and c-Myc in K1 PTC cells.

The results suggest that the cannabinoid-containing product BRF1A interacts as a potential regulator in well-differentiated thyroid cancer with the upregulation of p53 and downregulation of BLC-2 and c-Myc. Further in vitro and in vivo studies are needed to understand the exact mechanism and therapeutic potential of the cannabinoid-containing products in papillary thyroid cancer.

Heterogeneity of breast cancer poses several challenges for detection and treatment. With next-generation sequencing, we can now map the transcriptional profile of each patient's breast tissue, which has the potential for identifying and characterizing cancer subtypes. However, the large dimensionality of this transcriptomic data and the heterogeneity between the molecular profiles of breast cancers poses a barrier to identifying minimal markers and mechanistic consequences. In this study, we develop an autoencoder to identify a reduced set of gene markers that characterize the four major breast cancer subtypes with the accuracy of 82.38%. The reduced feature space created by our model captures the functional characteristics of each breast cancer subtype highlighting mechanisms that are unique to each subtype as well as those that are shared. Our high prediction accuracy shows that our markers can be valuable for breast cancer subtype detection and have the potential to provide insights into mechanisms associated with each subtype.

Breast cancer is the most prevalent malignancy among women globally. Molecular-targeted therapy improves treatment efficacy by precisely targeting tumor-specific molecules, minimizing damage to healthy tissues. Identifying new molecular targets is essential for enhancing therapeutic outcomes and prognosis in breast cancer.

The TCGA database was used to assess CD164 expression in breast cancer and its correlation with prognosis. Chemosensitivity analysis was performed to evaluate the association between CD164 and response to targeted therapies. Immune infiltration analysis was conducted to assess the relationship between CD164 expression and immune cell populations. CCK-8 assays, clonogenic assays, and flow cytometry analyses were employed to examine the effects of CD164 knockdown on cell viability, proliferation, cell cycle progression, and apoptosis. RNA sequencing and Gene Set Enrichment Analysis (GSEA) were performed to identify pathways regulated by CD164.

CD164 was highly expressed in breast cancer tissues and correlated with poorer prognosis, including shorter disease-free and overall survival. Chemosensitivity analysis linked CD164 to sensitivity to multiple targeted therapies, suggesting its role in oncogenic pathways. Immune infiltration analysis revealed CD164's association with immunosuppressive cells, including resting CD4 memory T cells, M2 macrophages, and mast cells, while exhibiting a negative correlation with Tregs and NK cells, underscoring its significance in the immunosuppressive tumor microenvironment. CD164 knockdown inhibited cell viability and proliferation and induced cell cycle arrest and apoptosis. RNA sequencing and GSEA showed that CD164 regulates proliferation, metabolism, migration, and adhesion pathways while suppressing tumor-promoting pathways and activating immune-related pathways.

CD164 plays a critical role in breast cancer progression, influencing tumor growth, immune evasion, and therapeutic response. It represents a promising therapeutic target, offering potential for improving breast cancer treatment and prognosis.

Inflammation is closely linked to the development and progression of cancer, as well as the effectiveness of cancer treatment. Inflammation is an immune response triggered when the immune system detects harmful stimuli such as pathogens, damaged cells, or toxic substances through pattern recognition receptors (PRRs). This activates signaling pathways and inflammasomes leading to the release of pro-inflammatory cytokines. In chronic inflammation, immune cells such as T and B lymphocytes, play a significant role in amplifying and sustaining the inflammatory response. The Inflammasomes are protein complexes that respond to microbes and danger signals, triggering an inflammatory response. Key inflammasomes, including NLRP3, AIM2, and NLRC4, regulate the release of proinflammatory cytokines and induce pyroptosis. While inflammasome activation is vital for immune defense, its dysregulation is associated with various diseases, including cancer. The relationship between inflammasomes and cancer is complex and varies depending on the context, with studies showing both promotion and inhibition of tumor growth. This review highlights the connection between microbes and radiation induced inflammatory regulators and cancer, stressing the need for research to understand the mechanisms through which inflammasomes and other inflammatory sensors control cancer.