Kaihui Sha

Background: Glioma is a highly heterogeneous and aggressive malignancy of the central nervous system, and reliable molecular biomarkers are urgently needed to improve prognostic stratification and guide therapeutic decision-making. The MEX3 family of RNA-binding proteins has been implicated in tumorigenesis and post-transcriptional regulation; however, their comprehensive roles in glioma remain poorly understood. Methods: Integrated bioinformatic analyses were performed using transcriptomic and clinical data from TCGA, CGGA, and GEO cohorts to evaluate the expression profiles, diagnostic and prognostic value, genetic alterations, molecular interactions, immune infiltration characteristics, and functional pathways associated with MEX3A, MEX3B, MEX3C, and MEX3D. Protein-protein interaction networks, gene set enrichment, and co-expression analyses were conducted to explore potential biological mechanisms. A MEX3-related prognostic risk model was constructed and validated in independent datasets. Drug sensitivity correlations were analyzed using public pharmacogenomic resources. In addition, in vitro experiments, including qRT-PCR, western blotting, proliferation, migration, and invasion assays, were performed in U251 and LN229 glioma cell lines to functionally validate the bioinformatic findings. Results: All four MEX3 family members were significantly upregulated in glioma tissues compared with normal controls and demonstrated strong diagnostic performance. Distinct prognostic patterns were observed, with MEX3D consistently identified as an independent predictor of poor overall, disease-specific, and progression-free survival. MEX3 genes were associated with diverse genetic alterations and were enriched in pathways related to RNA processing, cell cycle regulation, and cancer-associated signaling. Immune analyses revealed significant correlations between MEX3 expression and multiple immune cell populations as well as immune checkpoint molecules, suggesting potential roles in shaping the glioma immune microenvironment. A MEX3-related co-expression-based prognostic model showed robust survival-predictive ability and remained effective in external validation cohorts. Functional assays confirmed that silencing individual MEX3 genes significantly inhibited glioma cell proliferation, migration, and invasion in vitro . Conclusions: This study provides a comprehensive characterization of the MEX3 family in glioma, demonstrating their dysregulation, prognostic relevance, immune associations, and functional contributions to malignant phenotypes. Among them, MEX3D emerges as a particularly promising prognostic biomarker. These findings establish a foundation for future mechanistic and translational studies exploring MEX3 family members as potential biomarkers or therapeutic targets in glioma.

This study aims to investigate whether alpinetin prevents lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute liver injury (ALI) in mice by inhibiting ferroptosis, and to explore the potential molecular mechanisms involved. Thirty-six male BALB/c mice were randomly assigned to one of six groups (n = 6): the control group, the LPS/D-GalN group, the Ferrostatin-1 (Fer-1) + LPS/D-GalN group, and the alpinetin (12.5, 25, or 50 mg/kg) + LPS/D-GalN groups.The ferroptosis-specific inhibitor Fer-1 was used as a positive control to verify the involvement of ferroptosis in the injury. Following intraperitoneal (i.p.) administration of alpinetin (12.5, 25, or 50 mg/kg) for three consecutive days, acute liver injury was induced by an i.p. injection of LPS (30 µg/kg) and D-GalN (600 mg/kg). The effect of alpinetin on ALI was detected by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and hematoxylin and eosin (H&E) staining of hepatic tissue. Ferroptosis levels were analyzed by malondialdehyde (MDA), reduced glutathione (GSH), and Fe²⁺. In addition, the expression levels of ferroptosis-related proteins were determined by western blot and quantitative real-time PCR (qRT-PCR). The results show that alpinetin inhibited the increase of serum ALT and AST levels and hepatic tissue pathological damage induced by LPS/D-GalN. Alpinetin also inhibited ferroptosis by reducing MDA and Fe²⁺ levels and enhancing GSH activity. Simultaneously, alpinetin regulates iron metabolism-related proteins by inhibiting the expression of transferrin receptor 1 (TFR1) and divalent metal transporter 1 (DMT1) while promoting the expression of ferritin heavy chain (FTH). Additionally, alpinetin increased the expression of the ferroptosis-related protein nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Alpinetin protects against LPS/D-GalN-induced ALI by inhibiting the ferroptosis pathway, and its protective effect may depend on the activation of the Nrf2/SLC7A11/GPX4 axis.

Introduction The TOR signaling pathway regulator-like (TIPRL) gene plays a multifaceted role in cancer, yet its pan-cancer profile remains underexplored. This study investigates TIPRL expression across multiple cancers and its associations with survival, genetic alterations, immune infiltration, and functional pathways, providing insights into TIPRL’s role as a potential prognostic and therapeutic target. Methods TIPRL expression and prognostic significance across tumor types were analyzed using TCGA_GTEx and CPTAC data in R software and platforms like GEPIA2 and UALCAN. Genetic alterations and 3D structures were evaluated through cBioPortal. Associations with RNA modifications, immune checkpoints, immune cell infiltration, TMB, MSI, HRD, and enriched pathways were assessed via R and STRING databases, employing survival analysis, ssGSEA, and enrichment analyses. Results TIPRL expression was elevated in most cancers, with significant stage-specific associations observed in KICH, KIRP, and LUSC. High TIPRL expression correlated with worse overall survival in ACC, BRCA, HNSC, KICH, LIHC, and MESO, suggesting its role in prognosis. Genetic analysis identified amplifications as the main alteration, with varied clinical relevance across cancers. RNA modifications in TIPRL, particularly m1A, m5C, and m6A, suggested potential regulatory mechanisms. Immune infiltration analysis revealed TIPRL’s varied correlations with immune cell types and immune scores, differing by cancer type. TIPRL also positively correlated with TMB, MSI, and HRD in several cancers, indicating its association with genomic instability. Enrichment analyses highlighted TIPRL's involvement in processes like oxidative phosphorylation and autophagy, underscoring its influence in tumorigenesis. Conclusion These findings establish TIPRL as a significant biomarker in cancer progression and immune regulation, warranting further exploration into its therapeutic implications across diverse tumor types.

Purpose RING Finger 187 (RNF187) has recently emerged as a potential contributor to tumorigenesis. However, a comprehensive pan-cancer analysis of RNF187 in human tumors has not been undertaken until now. Methods Our study aims to investigate RNF187 expression across 33 different types of human tumors, utilizing data from the TCGA and GTEx databases. Results The pan-cancer analysis revealed significant upregulation of RNF187 in 27 types of cancers, contrasting with only low expression in LAML, with no statistical differences in OV and SARC. Notably, discernible associations were identified between RNF187 expression and the prognosis of cancer patients. Our investigation also unveiled correlations between RNA modification of RNF187 across various cancer types. Further exploration indicated a positive correlation between RNF187 levels and the presence of cancer-associated fibroblasts (CAFs) in numerous tumor types. Additionally, RNF187 exhibited correlations with a majority of immune inhibitory and stimulatory genes, as well as chemokines, receptors, MHC molecules, immunoinhibitors, and immunostimulators in various cancers. The findings highlighted associations between RNF187 expression and Tumor Mutational Burden (TMB), Microsatellite Instability (MSI) and Homologous Recombination Deficiency (HRD) in specific tumors. Finally, RNF187 showed a significant positive association with five genes (ALKBH4, FAM134A, MLST8, SANP47 and TMEM9) across the majority of tumors. GO enrichment and KEGG pathway analyses suggested that RNF187 may play a role in the pathogenesis of cancer through processes such as "bounding membrane of organelle," "macroautophagy," "proton-transporting V-type ATPase complex," "autophagy," "Ubiquitin mediated proteolysis," "Ferroptosis," "Phagosome," and etc. Conclusion Our inaugural pan-cancer study aims to provide a profound understanding of RNF187 in tumorigenesis across diverse types of tumors.

TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.