Biomedical subjects

Yifan Wang

Publications and source records attributed to Yifan Wang.

7 recordsLinked to original sources

PubMed2026

Joint Effects of Long-Term Obesity and Genetic Susceptibility on Sex-Specific Brain Aging.

OBJECTIVE: This study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex-specific brain aging. METHODS: We analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females). Sex-specific XGBoost models estimated multimodal brain age. We derived 16-year longitudinal obesity trajectories from repeatedly collected anthropometric measurements. Polygenic risk scores were constructed based on 55 independent genetic loci. Multivariable logistic regression examined associations of obesity trajectories and genetic risk with brain age acceleration. RESULTS: A total of 8198 (49.73%) males and 9089 (48.84%) females had accelerated brain aging. High genetic risk significantly increased brain age acceleration odds (males: OR = 1.39; females: OR = 1.34). Crucially, the high-stable obesity trajectory exerted a stronger effect in males (OR = 1.90, 95% CI: 1.64-2.21) than in females (OR = 1.25, 95% CI: 1.12-1.40), with the joint presence of high genetic risk and high-stable obesity amplifying risk to an OR of 2.78 in males and 1.57 in females. Conversely, shifting from obesity to non-obesity reduced risk by 30% in males and 18% in females. CONCLUSIONS: These findings underscore long-term obesity as a critical, sex-dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.

brain aging↗

PubMed2026

Epi-Allele elicits compensatory expression of the non-targeted allele and prevents haploinsufficiency in dominant genetic diseases.

Epigenetic regulation may underlie asymmetric allelic expression of many genes during development and disease pathogenesis. Allele-specific epigenetic modification could provide an efficient therapy for dominant genetic diseases due to heterozygous mutations. We developed an allele-specific epigenetic editing method ("Epi-Allele") for silencing pathogenic alleles and found surprisingly elevated expression of the non-targeted alleles, leaving total gene expression unchanged. Genome-wide screening revealed that such compensated allelic expression represents a common phenomenon, suggesting that the Epi-Allele approach could avoid the haploinsufficiency induced by current allele-specific silencing therapies. This notion was validated by allele-specific epigenetic remodeling of Myh6 and MYH7 genes in ameliorating cardiac phenotypes in a hypertrophic cardiomyopathy (HCM) mouse model and HCM patient iPSC-derived cardiomyocytes, respectively. Thus, Epi-Allele offers an allele-specific haploinsufficiency-free therapeutic approach for treating dominant genetic diseases.

DNA methylation↗

PubMed2026

Integrated transcriptomic and immunogenomic analysis unravels the immunological functions and prognostic landscape of WD repeat domain 76.

BackgroundWD Repeat Domain 76 (WDR76) plays a potential role in cellular regulation; however, its comprehensive landscape across human malignancies and its specific biological function in hepatocellular carcinoma (HCC) remain largely unexplored.MethodsWe conducted a systematic pan-cancer analysis utilizing multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) atabases to evaluate WDR76 expression, subcellular localization, and its correlation with clinicopathologic features, genomic instability, and immune infiltration. Diagnostic and prognostic values were assessed via Receiver operating characteristic (ROC) and Kaplan-Meier analyses. Furthermore, the functional role of WDR76 in HCC was validated in vitro using Hep-3B and Huh7 cell lines through siRNA-mediated knockdown, followed by CCK-8, wound-healing, and transwell assays.ResultsWDR76 was significantly upregulated in the majority of tumor types, including LIHC, LUAD, and COAD, while exhibiting nuclear localization. Elevated WDR76 expression correlated with advanced tumor staging, metastasis, and poor clinical outcomes across multiple cohorts, particularly in ACC, KIRP, and LIHC. ROC analysis highlighted its exceptional diagnostic precision in cancers such as GBM and LIHC. Immunologically, WDR76 expression was intricately linked to immune cell infiltration, immune checkpoint markers, and genomic instability parameters, suggesting a role in shaping the tumor microenvironment. Drug sensitivity profiling revealed that high WDR76 levels correlate with resistance to specific chemotherapeutic agents. Experimentally, silencing WDR76 in HCC cells significantly suppressed cell proliferation, migration, and invasion capabilities.ConclusionOur study establishes WDR76 as a robust pan-cancer prognostic biomarker and a potential immunotherapeutic target. Specifically, we provide experimental evidence that WDR76 functions as an oncogenic driver in liver cancer, promoting malignant phenotypes and offering a novel avenue for targeted therapeutic intervention.

Humans↗

PubMed2026

Genome-Wide Characterization of the ZIP Transporter Family in Sea Island Cotton (Gossypium barbadense L.) and Expression Profiling Under Heavy Metal and Pathogen Stresses.

G. barbadense represents an indispensable germplasm resource for high-quality textile fiber and disease resistance; nevertheless, systematic information regarding its ZRT/IRT-like protein (ZIP) gene family remains limited. Here, a total of 46 GbZIP genes were identified across the G. barbadense genome. Comprehensive bioinformatic investigations revealed uneven chromosomal distribution and confirmed that segmental/whole-genome duplications, supplemented by localized tandem duplications, drove family expansion. Members clustered within the same phylogenetic clades shared conserved motif organization and gene architecture, while promoter regions harbored abundant cis-acting elements associated with phytohormone and stress signaling. Transcriptome profiling indicated distinct expression patterns across vegetative/reproductive tissues, fiber and ovule developmental stages, and diverse abiotic stress conditions (cold, hot, drought, and salt). Quantitative Real-Time PCR (qRT-PCR) further validated that several GbZIP candidates exhibited temporal expression variations upon exposure to cadmium toxicity, V. dahliae infection, and combined Cd-V. dahliae stress. Specifically, GbZIP13, GbZIP18, GbZIP27, and GbZIP36 displayed prominent broad-spectrum responses to all three stress conditions, whereas GbZIP16, GbZIP29, and GbZIP30 showed stress-specific regulatory divergence. Overall, this study aims to systematically analyze the evolutionary characteristics and expression patterns of the GbZIP family, and to specifically evaluate the response differences under Cd stress, V. dahliae stress, and combined stress, in order to identify potential key candidate genes.

Gossypium barbadense↗

PubMed2026

POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma.

OBJECTIVE: Protein O-fucosyltransferase 1 (POFUT1) has been implicated in several malignancies, but its functional and prognostic significance in glioma remains insufficiently defined. This study evaluated whether POFUT1 expression is associated with glioma progression, patient outcome, and PI3K/AKT pathway activity. METHODS: Public glioma transcriptome datasets from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) were analyzed and compared with clinical samples collected from 123 glioma patients. POFUT1 protein levels in clinical specimens were determined by immunohistochemical staining, and its association with patient outcome was analyzed using survival curves. In vitro, glioma cell growth, motility, and invasiveness were examined using MTT and Transwell assays. The effect of POFUT1 on tumor formation was further tested in a subcutaneous xenograft model. RNA sequencing, KEGG pathway enrichment, and pharmacological inhibition were then used to explore the mechanism linking POFUT1 to PI3K/AKT signaling. RESULTS: POFUT1 expression was higher in glioma than in normal brain tissue and increased with tumor grade. Patients with high POFUT1 levels had shorter overall survival, and multivariate Cox analyses supported POFUT1 as an independent prognostic indicator. Incorporating POFUT1 into a nomogram improved prediction of 1-, 3-, and 5-year survival. Functionally, POFUT1 knockdown reduced glioma cell growth, motility, invasion, and xenograft expansion, whereas POFUT1 overexpression produced the opposite phenotype. Transcriptomic and protein analyses indicated that POFUT1 enhanced PI3K/AKT signaling. The PI3K inhibitor LY294002 weakened the tumor-promoting effects caused by POFUT1 overexpression. CONCLUSION: POFUT1 as a key driver of glioma malignancy, predominantly through activating the PI3K-AKT signaling pathway. These findings highlight POFUT1 as a promising novel therapeutic target for aggressive glioma.

Glioma↗

PubMed2025

Design of optimized epigenetic regulators for durable gene silencing with application to PCSK9 in nonhuman primates.

Epigenetic editing is a promising strategy for modifying gene expression while avoiding the permanent alterations and potential genotoxicity of genome-editing technologies. Here we designed optimized epigenetic regulators (EpiRegs) by testing combinations of transcription activator-like effector (TALE)-based and catalytically deactivated Cas9 (dCas9)-based epigenetic modification effectors and fusion protein structures. TALE-based EpiReg (EpiReg-T) achieved a final efficiency of 98% in mice, surpassing the initial dCas9-based efficiency of 64%. We demonstrated the approach in macaques by introducing DNA methylation and histone modifications to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, thereby lowering low-density lipoprotein cholesterol levels. A single dose of EpiReg-T delivered with lipid nanoparticles achieved efficient (>90%) and long-lasting (343 days) silencing of PCSK9 in the liver. Integrative multiomic analyses revealed minimal off-target effects in EpiReg-T-treated monkeys, mice and human-derived cells. EpiReg can be redirected to other genes by reengineering the DNA-binding domain. Our findings represent a step toward the clinical application of epigenetic editing for the treatment of human diseases.

Animals↗

PubMed2024

LINC00887 promotes GCN5-dependent H3K27cr level and CRC metastasis via recruitment of YEATS2 and enhancing ETS1 expression.

Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.

Humans↗