Ask about this productRelated genes to: PHLDA3 Blocking Peptide
- Gene:
- PHLDA3 NIH gene
- Name:
- pleckstrin homology like domain family A member 3
- Previous symbol:
- -
- Synonyms:
- TIH1
- Chromosome:
- 1q32.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-19
- Date modifiied:
- 2016-10-05
Related products to: PHLDA3 Blocking Peptide
Related articles to: PHLDA3 Blocking Peptide
- Obesity disrupts skeletal muscle metabolism through insulin resistance, oxidative stress, and ectopic fat deposition, yet transcriptomic findings across individual studies remain inconsistent. We performed a meta-analysis of four independent RNA sequencing (RNA-seq) studies of human vastus lateralis muscle, comparing 29 individuals with obesity (body mass index (BMI) ≥ 30 kg/m) and 23 with normal weight. Differential expression was analyzed using DESeq2, with age and sex included as covariates in studies where individual-level data were available. Study-level results were integrated using the direction-aware inverse normal method (weighted Stouffer). Between-study heterogeneity was assessed by gene-level I statistics derived from random-effects meta-analysis of log fold changes. Functional annotation was performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The weighted Stouffer method identified 2136 differentially expressed genes (DEGs) (adjusted < 0.05), comprising 1028 upregulated and 1108 downregulated genes, of which 674 (31.6%) were detected only through the meta-analysis. Three genes- (down), (down), and (up)-were significant in every individual study and in the combined analysis. Downregulated DEGs were enriched in cytoplasmic translation, ribosomal structure, and oxidative phosphorylation, whereas upregulated DEGs were associated with extracellular matrix organization and the focal adhesion pathway. This RNA-seq meta-analysis of skeletal muscle in obesity identifies robust DEGs and dysregulated pathways, providing candidate targets for future mechanistic and translational research. - Source: PubMed
Publication date: 2026/03/15
Wang YuhaoLi HanLi YixuanKong WenLi Yuming - UFMylation, a recently identified ubiquitin-like modification mediated by the E3 ligase UFL1, plays context-specific roles in cancers, but its substrates and functions in lung adenocarcinoma (LUAD) remain poorly defined. Here, we identify the AKT signaling repressor PHLDA3 as a substrate of UFL1 in LUAD. UFMylation of PHLDA3 at Lys51 and Lys106 promotes its membrane localization, thereby blocking AKT membrane recruitment and suppressing downstream signaling. Tumor-associated PHLDA3 mutations F41L, E82G, and K106N impair its UFMylation and membrane translocation, resulting in AKT hyperactivation and enhanced tumor growth. In samples from patients with LUAD, UFL1 expression inversely correlates with phospho-AKT levels. Functionally, the UFL1-PHLDA3 axis inhibits LUAD progression in both cell line-based and patient-derived xenograft models. These findings define a tumor-suppressive UFMylation pathway that modulates AKT activity and provides a mechanistic rationale for targeting UFL1-PHLDA3 signaling in LUAD. - Source: PubMed
Publication date: 2026/03/25
Ma XiuqingWan RuiYang XiaoTang JiaxinWen YaleiHuang LeiLi XinyingSong YanZhou YangWang Shao-HuaLiu Tongzheng - Doxorubicin (DOX) is an effective chemotherapeutic agent whose clinical utility is limited by cardiotoxicity. To investigate underlying mechanisms, we employed a multi-omics approach integrating transcriptomics and proteomics, leveraging established mouse models of chronic DOX-induced cardiotoxicity. : Five-week-old male mice received weekly DOX (4 mg/kg) or saline injections for six weeks, with heart tissues harvested 4 days post-treatment. Differentially expressed genes (DEGs) and proteins (DEPs) were identified by bulk RNA-seq and proteomics, validated via qPCR and Western blot, respectively. Key DEPs were validated in plasma samples from DOX-treated breast cancer patients. Additionally, temporal comparison was conducted between DEPs in the mice hearts 4 days and 6 weeks post-DOX. : RNA-seq revealed upregulation of stress-responsive genes (, ) and circadian regulators (), with downregulation of and . Proteomics identified upregulation of serpina3n, thrombospondin-1, and epoxide hydrolase 1. Plasma SERPINA3 concentrations were significantly elevated in breast cancer patients 24 h post-DOX. Gene set enrichment analysis (GSEA) revealed upregulated pathways, including p53 signaling, apoptosis, and unfolded protein response. Integrated omics analysis revealed 2089 gene-protein pairs. GSEA of concordant gene-protein pairs implicated p53 signaling, apoptosis, and epithelial-mesenchymal transition in upregulated pathways, while oxidative phosphorylation and metabolic pathways were downregulated. Temporal comparison with a delayed timepoint (6 weeks post-DOX) uncovered dynamic remodeling of cardiac signaling, with early response dominated by inflammatory and apoptotic responses, and delayed response marked by cell cycle and DNA repair pathway activation. : This integrated omics study reveals key molecular pathways and temporal changes in DOX-induced cardiotoxicity, identifying potential biomarkers for future cardioprotective strategies. - Source: PubMed
Publication date: 2026/01/29
Dabour Mohamed SAbdelgawad Ibrahim YSadaf BushraDaniel Mary RGrant Marianne K OBlaes Anne HJacobson Pamala AZordoky Beshay N - Computed tomography (CT) is a major source of low-dose ionizing radiation exposure in medical imaging. Risk assessment at this dose level is difficult and relies on the hypothetical linear no-threshold model. To address the response to such low doses in patients undergoing CT scans, we examined radiation-induced alterations at the transcriptomic and DNA damage levels in peripheral blood cells. Peripheral whole blood of 60 patients was collected before and after CT. Post-CT samples were obtained 4-6 h after scan (n = 28, in vivo incubation) or alternatively immediately after the CT scan, followed by ex vivo incubation (n = 32). The gene expression of known radiation-responsive genes (n = 9) was quantified using qRT-PCR. DNA double-strand breaks (DSB) were assessed in 12 patients through microscopic γ-H2AX + 53BP1 DSB focus staining. The mean dose-length product (DLP) across all scans was 561.9 ± 384.6 mGy·cm. Significant differences in the median differential gene expression (DGE) were detected between in vivo and ex vivo incubation conditions, implicating that ex vivo incubation masked the true effect in low-dose settings. The median DGE of in vivo-incubated samples showed a significant upregulation of , , , , , and ( ranging from <0.001 to 0.041). In vivo, we observed a linear dose-dependent upregulation for several genes and an explained variance of 0.66 and 0.56 for and , respectively. DSB focus analysis revealed a slight, non-significant increase in the average DSB damage post-exposure, at a mean DLP of 321.0 mGy·cm. Our findings demonstrate that transcriptional biomarkers are sensitive indicators of low-dose radiation exposure in medical imaging and could prove themselves as clinically applicable biodosimetry tools. Furthermore, the results underscore the need for dose optimization. - Source: PubMed
Publication date: 2025/12/09
Schmid NikolaiGorte VadimAkers MichaelVerloh NiklasHaimerl MichaelStroszczynski ChristianScherthan HarryOrben TimoStewart SamanthaKubitscheck LauraKaatsch Hanns LeonhardPort MatthiasAbend MichaelOstheim Patrick - In colorectal cancer, approximately 50% to 70% of metastases go into the liver; however, their molecular signature remains unknown. We aimed to investigate the transcriptome and miRNome profiles of metachronous colorectal liver metastasis (mCLM) within the hepatic microenvironment and to identify key deregulated genes, microRNAs (miRNAs), pathways, and their clinical relevance. We performed differential expression analysis on 36 mCLM and adjacent nonmalignant liver tissue pairs using RNA sequencing. Gene set enrichment analysis and consensus molecular subtype (CMS) classification helped to explore pathways. Tumor samples were stratified based on their KRAS mutation status. miRNA-mRNA interactions were investigated through coexpression and correlation analysis, with prognostic relevance assessed using survival analysis. Validation of key interactions was accomplished using multiMiR. We identified 1809 upregulated and 1639 downregulated genes and 108 upregulated and 92 downregulated miRNAs in mCLM compared with the adjacent nonmalignant liver. Upregulated genes were associated with epithelial-to-mesenchymal transition, G2M checkpoints, and E2F targets. About 47% of samples belonged to CMS2 and 22% to mesenchymal CMS4, with distinct mutational patterns. mRNA coexpression identified 4 clusters (associated with metabolism, cell cycle, DNA metabolism, and oncogenic signaling pathways), and miRNA coexpression identified 6 clusters. The hub miRNAs hsa-let-7c, hsa-miR-21-5p, hsa-miR-106a-5p, hsa-miR-139-5p, hsa-miR-101-3p, and hsa-miR-20b-5p were among the inversely correlated miRNA-mRNA clusters. An integrative analysis highlighted PEA15 interaction with hsa-miR-320b/c, TEX2/CTSO with hsa-miR-103a-3p, and PHLDA3 with hsa-miR-1304, and prognostic relevance for ZNF441, CTSO, TEX2, EID1, CMC1, hsa-miR-4634, hsa-miR-3184-5p, has-miR-320b, hsa-miR-1304-3p, hsa-miR-7-1-3p, hsa-miR-144-3p, hsa-miR-1303, and hsa-miR-660-3p. The miRNA-mRNA interactions were validated using real-time PCR in independent patient cohorts. This study revealed a complex molecular landscape of mCLM within the hepatic microenvironment and novel miRNA-mRNA interactions with potential prognostic and therapeutic implications. - Source: PubMed
Publication date: 2025/12/19
Rao Bhavana HemanthaBoušková VeronikaHeczko LucieHolý PetrŠeborová KarolínaLiška VáclavVyčítal OndřejFiala OndřejSouček PavelHlaváč Viktor