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Results for “CRYAB”

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3 recordsLinked to original sources
PubMed2026

Integrative Multi-Omics Analysis Identifies Thrombosis-Associated Molecular Features Linked to Germline Susceptibility and Immune Cell Communication in Gastric Cancer.

Emerging evidence indicates that coagulation-related molecular programs are associated with thrombosis, tumor progression, and molecular dysregulation in gastric cancer (GC). However, thrombosis-associated molecular features in GC and their potential links to inherited susceptibility remain insufficiently understood. Integrated analyses of transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were performed to identify thrombosis-associated genes and establish a machine learning-based prognostic signature. Genome-wide association study (GWAS), expression quantitative trait loci (eQTL), transcriptome-wide association study (TWAS), and Mendelian randomization (MR) analyses were conducted to investigate susceptibility-associated transcriptional programs in GC. Functional assays were used to evaluate candidate genes associated with malignant phenotypes. Single-cell RNA sequencing (scRNA-seq) and cell-cell communication analyses were further performed to characterize cell-type-specific expression patterns and potential intercellular interactions. A total of 22 differentially expressed thrombosis-associated genes were identified, and a prognostic signature comprising 14 genes was established. The signature stratified patients into high- and low-risk groups and showed prognostic performance in both the training and validation cohorts. Integrative GWAS, eQTL, and TWAS analyses identified susceptibility-associated transcriptional programs that were positively correlated with the thrombosis-associated risk score. Silencing ACTN2 and CRYAB significantly reduced GC cell migration and invasion. scRNA-seq analysis revealed relatively high CRYAB expression in neutrophils, and CellChat analysis suggested potential neutrophil-B cell interactions involving COLLAGEN-related signaling. This integrative multi-omics study identified a thrombosis-associated molecular signature linked to prognosis and germline susceptibility-associated transcriptional programs in GC. ACTN2 and CRYAB may represent candidate genes associated with GC cell migration and invasion, while single-cell analysis suggested potential immune-related communication features.

Humans↗
PubMed2025

Homeobox protein MSX-1 restricts hepatitis B virus by promoting ubiquitin-independent proteasomal degradation of HBx protein.

Hepatitis B virus (HBV) X protein (HBx) is a key factor for regulating viral transcription and replication. We recently characterized homeobox protein MSX-1 (MSX1) as a host restriction factor that inhibits HBV gene expression and genome replication by directly binding to HBV enhancer II/core promoter (EnII/Cp) and suppressing its promoter and enhancer activities. Notably, HBx expression was observed to be repressed more drastically by MSX1 compared to other viral antigens. In this work, we report that in addition to transcriptional repression, MSX1 also post-transcriptionally downregulates HBx protein stability. Mechanistically, MSX1 induces ubiquitin-independent proteasomal degradation of HBx, which is mediated through HBx C-terminal domain. Furthermore, this effect on HBx degradation correlates with MSX1-induced upregulation of DNAJA4 and CRYAB expression. Similar to MSX1, both DNAJA4 and CRYAB promote HBx degradation and repress HBV gene expression and genome replication. In chronic hepatitis B (CHB) patients, immune active phase (IA) is associated with higher intrahepatic expression of MSX1, DNAJA4 and CRYAB, and lower serum HBV markers compared to immune tolerant (IT) phase. Finally, HBV infection is significantly suppressed by MSX1 overexpression in both NTCP-overexpressing cell and humanized liver mouse models. These results demonstrate additional and novel mechanisms of MSX1-mediated repression of HBV, and establish MSX1 as a multi-functional HBV restriction factor with therapeutic potential.

Humans↗
PubMed2026

Integrated Multi-Omics Analysis Reveals the Genetic Basis of Phenotypic Variation in Tibetan Sheep.

Body size is a key economic trait influencing the profitability of farmed animals. This study used genome-wide association studies (GWAS) to identify five single nucleotide polymorphisms (SNPs) significantly associated with body size in the Tibetan sheep population, advancing molecular breeding and providing a basis for genomic selection. These SNPs are located within five candidate genes. SNaPshot validated GWAS results, demonstrating significant correlations between candidate SNPs and body size traits in Tibetan sheep. Concurrently, hematoxylin and eosin staining, alongside muscle fiber analysis, confirmed pronounced morphological differences in muscle tissue between sheep of varying conformation. Therefore, transcriptome and proteomics were performed on the longest dorsi muscle from large and small Tibetan sheep of both sexes. The transcriptome, together with weighted gene co-expression network analysis (WGCNA), identified VEPH1 and PRKG1 as core genes regulating body characteristics in Tibetan sheep through their involvement in the PI3K-Akt signaling pathway and pathways related to fat deposition. The integrative analyses demonstrated significantly different expression of CARNS1 and CRYAB at both transcriptional and protein levels between the muscles of large- and small-sized Tibetan sheep of both sexes, suggesting their importance in body size traits by influencing muscle morphology. This study provides valuable genomic resources that advance sheep genetics research.

GWAS↗