IQGAP3 promotes the progression of glioma as an immune and prognostic marker.

Background: IQGAP3 plays a crucial role in regulating cell proliferation, division, and cytoskeletal organization. Abnormal expression of IQGAP3 has been linked to various tumors, but its function in glioma is not well understood. Methods: Various methods, including genetic differential analysis, single-cell analysis, ROC curve analysis, Cox regression, Kaplan-Meier analysis, and enrichment analysis, were employed to analyze the expression patterns, diagnostic potential, prognostic implications, and biological processes involving IQGAP3 in normal and tumor tissues. The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence. Additionally, the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3. Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms. Results: High IQGAP3 expression in gliomas is associated with an unfavorable prognosis, particularly in wild-type IDH and 1p/19q non-codeleted gliomas. Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle, PI3K/AKT signaling, p53 signaling, and PLK1-related pathways. Furthermore, IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma. BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy. In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells, with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression. Conclusion: IQGAP3 shows promise as a valuable biomarker for diagnosis, prognosis, and immunotherapeutic strategies in gliomas.

A Comprehensive Analysis of the Prognostic, Immunological and Diagnostic Role of CCNF in Pan-cancer.

Background: Cyclin F (CCNF) represents a pivotal constituent within the family of cell cycle proteins, which also belongs to the F-box protein family and acts as a critical regulatory factor in cell cycle transition. Its heightened expression has been consistently identified across various cancer types, including breast, pancreatic, and colorectal cancer. Nonetheless, a comprehensive exploration of CCNF's involvement in pan-cancer remains lacking. Methods: This study collected transcriptomic data and clinical information from several databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and BioGPS detabase. Employing bioinformatics methods, we investigated the potential oncogenic role of CCNF, utilizing various databases such as cBioPortal, Human Protein Atlas (HPA), TIMER2, UALCAN, GEPIA, GSCALite, and CTD detabase. These analyses focused on exploring CCNF expression, prognosis, gene mutations, immune cell infiltration, DNA methylation levels, and targeted chemical drugs across different tumor types. Additionally, we obtained CCNF-related genes from GeneMANIA and GEPIA databases and conducted GO and KEGG enrichment analyses to gain deeper insights into the biological processes associated with CCNF. Furthermore, we validated the differential expression of CCNF in normal human breast cancer and breast cancer cell lines using experimental verification. Results: CCNF exhibited upregulation in the majority of cancer types, demonstrating early diagnostic potential in 15 cancers and prognostic implications for adverse outcomes across numerous malignancies. Furthermore, CCNF was found to be linked with markers of the tumor immune microenvironment in various cancers. Additionally, CCNF expression influenced genetic alterations in pan-cancer. Enrichment analysis revealed that CCNF primarily participates in crucial biological pathways such as the cell cycle, p53 signaling pathway, and cellular senescence pathways. RT-qpcr and WB assays further confirmed that CCNF expression was higher in human cancer cell lines than in normal cell lines. Conclusion: The underlying role and mechanism of CCNF in pan-cancer were elucidated through comprehensive bioinformatics analysis and experimental validation. CCNF holds promise as an invaluable early detection indicator and tumor biomarker, offering potential targets for tumor treatment and prevention.

Isobavachalcone's Alleviation of Pyroptosis Contributes to Enhanced Apoptosis in Glioblastoma: Possible Involvement of NLRP3.

Glioblastoma multiforme (GBM) is the most malignant intracranial tumor with high mortality rates and invariably poor prognosis due to its limited clinical treatments. There is an urgent need to develop new therapeutic drugs for GBM treatment. As a natural prenylated chalcone compound, Isobavachalcone (IBC)'s favorable pharmacological activities have been widely revealed. However, potential inhibitory effects of IBC on GBM have not been explored. In the present study, we aimed to detect the effects of IBC on GBM and clarify its anti-GBM mechanisms for the first time. It was observed that IBC could inhibit GBM cell proliferation, migration, and invasion in vitro and prevent tumor growth without any significant drug toxicity in both subcutaneous and orthotopic GBM xenograft tumor models in vivo. Mechanistically, IBC may target NOD-like receptor family pyrin domain-containing 3 (NLRP3) transcription factor estrogen receptor α (ESR1 gene) by network pharmacology and molecular docking analysis. Experimentally, IBC alleviated NLRP3 inflammasome-related pyroptosis and inflammation, arrested cell cycle at G1 phase, and induced mitochondria-dependent apoptosis in GBM cells. IBC's inhibition on NLRP3 could be rescued by the NLRP3 antagonist CY-09 both in vitro and in vivo. These results indicate that IBC is a potential therapeutic drug against GBM and provide a new insight into GBM treatment.