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Introduction: Glioma, particularly glioblastoma (GBM), is a highly malignant brain tumor with poor prognosis despite current therapeutic approaches. The tumor microenvironment (TME), plays a crucial role in glioma progression by promoting invasion and drug resistance. Angiogenesis, the formation of new blood vessels, is a tightly regulated process involving endothelial cell activation, proliferation, and migration. In cancer, angiogenesis becomes dysregulated, leading to excessive blood vessel formation. Methods: We enrolled bulk data of TCGA-LGG/GBM, CGGA-693, and CGGA-325 cohorts, scRNA data of GSE162631, GSE84465, and GSE138794 cohorts. Identification of malignant cells was conducted by "copycat" R package. The "AUCell" R package scored the activity of target gene set of each single cell. Consensus clustering was applied using the "ConsensusClusterPlus" R package, while tumor-infiltrating immune cells were determined using "IOBR" R package. To construct a prognostic model, we used LASSO and multiCOX algorithms based on the expression levels of the 15 hub genes, the efficacy of which was verified by KM and ROC analysis. Results: We identified 4 different malignant cell subclusters in glioma and disclosed their distinct gene expression patterns and interactions within TME. We identified differentially expressed immune-related genes (DE-ARGs) in glioma and found 15 genes that were specifically expressed in the malignant glioma cell populations. Glioma cells with higher expression of these DE-ARGs were associated with gliogenesis, glial cell development, and vasculature development. We found that tumor-infiltrating monocytes were the main interacting cell type within glioma TME. Using the expression patterns of the 15 screened DE-ARGs, we categorized glioma samples into 2 molecular clusters with distinct immune features, suggesting a possible relationship between angiogenesis and immune activation and recruitment. We constructed a prognostic model based on the expression levels of the 15 DE-ARGs and evaluated its predictive ability for glioma patient outcomes, which displayed exceedingly high efficacy. Conclusion: We characterized different malignant cell subclusters in glioma and investigate their gene expression patterns and interactions within TME. We constructed a prognostic model based on the expression levels of the 15 DE-ARGs and evaluated its predictive ability for glioma patient outcomes, which displayed exceedingly high efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Cervical cancer (CC) ranks as the fourth most prevalent malignancy among women worldwide, necessitating effective therapeutic interventions to mitigate its detrimental impact on both physical and mental health. Parthenolide (PTL), a natural product of the sesquiterpene lactone derived from Feverfew leaves, has exhibited promising anti-tumor properties in previous studies; however, its precise effects and underlying molecular mechanisms in CC remain elusive. Methods: In this work, we investigated the effect of PTL on the proliferation and migration of CC cells. Western blot analysis and Reverse transcription‑quantitative PCR were used for mechanistic elucidation. Results: Our findings indicated that PTL substantially inhibited the proliferation of HeLa and SiHa CC cell lines in a dose- and time-dependent manner. Moreover, PTL significantly suppressed the migration of CC cells by down-regulating the expression of vascular endothelial growth factor (VEGF), metastasis-associated protein 1 (MTA1), and transforming growth factor-β1 (TGF-β1). Mechanistically, PTL blocked the phosphorylation of focal adhesion kinase (FAK) and glycogen synthase kinase-3β (GSK3β) induced by epidermal growth factor (EGF). Further investigations revealed that PTL suppressed the proliferation of CC cells by inhibiting the EGF-mediated phosphorylation of the FAK/GSK3β signaling pathway. Conclusion: Taken together, the present in vitro results suggest that PTL may inhibit the proliferation and migration of CC cells through down-regulating the FAK/GSK3β signaling pathway, providing new insights for the application of PTL in the treatment of CC. [ABSTRACT FROM AUTHOR]

Dysregulation of autophagy in cancer-associated fibroblasts (CAFs) has been demonstrated to play a role in malignant phenotypes of human tumors. We intended to investigate the function of CAFs autophagy in prostate cancer (PCa). Firstly, CAFs and normal fibroblasts (NFs) were isolated from cancerous and adjacent normal tissues of PCa patients, for the following experimental preparation. In comparison with NFs, CAFs expressed higher levels of the myofibroblast marker ?-smooth muscle actin (?-SMA) and the mesenchymal marker Vimentin. Besides, CAFs possessed a higher autophagic level than NFs. As for malignant phenotypes, PCa cells co-cultured with CAFs-CM showed greater proliferation, migration and invasion capabilities, while these outcomes were obviously abolished by autophagy inhibition with 3-Methyladenine (3-MA). Moreover, silencing of ATG5 in CAFs inhibited fibroblasts autophagic level and suppressed malignant phenotypes of PCa cells, while ATG5 overexpression in NFs exerted opposite effects. Depletion of ATG5 in CAFs inhibited the xenograft tumor growth and lung metastasis of PCa cells. Taken together, our data demonstrated the promotive effect of CAFs on PCa malignant phenotypes through ATG5-dependent autophagy, suggesting a novel mechanism for PCa progression. [ABSTRACT FROM AUTHOR]