Identification of fatty acid metabolism-related genes in the tumor microenvironment of breast cancer by a development and validation of prognostic index signature

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: April 7, 2025

Abstract Background Breast cancer (BRCA) is a malignancy originating in the breast cells, characterized by poor overall survival rate. Post-resection, chemotherapy commonly recommended as primary therapeutic approach; however, its efficacy remains limited. Recent advancements lipidomics and metabolomics have provided new insights into intricate landscape of fatty acid metabolism (FAM) lipidome both health disease. A growing body evidence suggests that dysregulations FAM levels play significant role initiation progression. Despite these advances, precise mechanisms through which mediates anti-cancer effects lobaplatin BRCA remain poorly understood warrant further investigation. Methods GEO TCGA data were classified two types. We aimed to show how FAMGs influence immune function, checkpoints, m6a BRCA. co-expression analysis discovered gene expression strongly connected pyroptosis. The gathered information about mRNAsi, mutations, CNV, clinical features. Results In low-risk group, (OS) longer. GSEA was utilized identify tumor-related pathways. Most FAMG-derived prognostic signatures predominantly modulate immunological oncogenic signaling pathways, including Wnt, neurotrophin, chemokine, calcium cascades. Among genes involved are CEL, WT1, ULBP2. Expression varied well. model, CNVs, single nucleotide polymorphism (SNP), drug sensitivity all pointed gene. Conclusions objective this study validate BRCA-associated can serve indicators provide system while also offering support development metabolism-related molecularly targeted therapeutics. Consequently, their interactions with system, well BRCA, may emerge promising targets.

Language: Английский

TBCK-deficiency leads to compartment-specific mRNA and lysosomal trafficking defects in patient-derived neurons

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

ABSTRACT Monogenic pediatric neurodegenerative disorders can reveal fundamental cellular mechanisms that underlie selective neuronal vulnerability. TBCK-Encephaloneuronopathy (TBCKE) is a rare autosomal recessive disorder caused by stop-gain variants in the TBCK gene. Clinically, patients show evidence of profound neurodevelopmental delays, but also symptoms progressive encephalopathy and motor neuron disease. Yet, physiological role protein remains unclear. We report human TBCKE model, derived from iPSCs homozygous for Boricua variant (p.R126X). Using unbiased proteomic analyses neurons, we find interacts with PPP1R21, C12orf4, Cryzl1, consistent being part FERRY mRNA transport complex. Loss leads to depletion C12ORF4 levels across multiple cell types, suggesting may play regulating at least some members preferentially, not exclusively, localizes surface endolysosomal vesicles colocalize lysosomes. Furthermore, TBCK-deficient neurons have reduced content axonal compartment relative soma. lysosomal dynein/dynactin adapter JIP4, which functionally exhibiting striking retrograde trafficking defects. Hence, our work reveals mediate mRNA, particularly along lysosomes compartments. TBCK-deficiency compartment-specific defects likely contribute preferential susceptibility neurodegeneration.

Language: Английский

The Dynamic Landscape of 3′‐UTR Alternative Polyadenylation Across Mouse Fetal Development and Anatomy

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Alternative cleavage and polyadenylation (APA) in the 3'-untranslated region (3'-UTR) of mRNA produces transcripts with varied 3'-UTR plays a key role development organogenesis. This work characterizes APA using 85 high-quality RNA-seq datasets encompassing 12 tissue types eight developmental stages mouse fetuses. Results show that 46.4% expressed genes undergo tissue-specific manner. Changes site (pAS) usage often operate beyond transcriptional control, revealing as an additional layer gene regulation. Sequence analysis demonstrates pAS selection, governed by signal strength adenine preferences, is evolutionarily conserved between mice humans. Intriguingly, brain tissues display complex dynamics during development, potentially regulated RNA-binding proteins such Rbm38, impacting 3' UTR extension restricting distal usage. These events are associated depletion miRNA binding sites enrichment transposable elements within alternative UTRs. To facilitate further research, this develops APApedia (http://xozhanglab.com/apapedia/), comprehensive database cataloging identified events, which serves valuable resource for community to study aids deciphering functional implications fetal development.

Language: Английский