Biomedical subjects

Jing-Ping Yun

Publications and source records attributed to Jing-Ping Yun.

2 recordsLinked to original sources

PubMed2025

Genomic and Transcriptomic Landscape of Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma: A Multicenter Study.

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is a rare indolent malignant neoplasm, which occurs almost exclusively in the liver or spleen and may arise from a common EBV-infected mesenchymal cell that differentiates along the follicular or fibroblastic dendritic cell pathway. Despite its rarity, it presents a pressing need for an improved understanding of its genetic underpinnings and potential treatment strategies for recurrent or disseminated cases. To address this, we conducted comprehensive whole-exome sequencing and transcriptome sequencing (mRNA-seq) analyses on 31 and 6 cases of EBV+ IFDCS, respectively, collected from multiple centers in China. We also compared the genetic features of EBV+ IFDCS with those of other EBV-associated malignancies. Our analyses revealed a relatively high somatic mutation rate and widespread copy number variations affecting the major histocompatibility complex-I/II in EBV+ IFDCS. Integrated mutational profiling identified key signaling pathways involved in epigenetic regulation, NF-κB signaling, RTK/RAS/PI(3)K, and the Hippo pathway. Furthermore, we identified several frequently altered genes that could serve as potential therapeutic targets in EBV+ IFDCS. Transcriptomic analysis unveiled significant upregulation of pathways related to virus infection, immune responses, and multiple immune checkpoint genes in EBV+ IFDCS. Comparative analysis demonstrated clear genetic distinctions between EBV+ IFDCS and other EBV-associated tumors. In conclusion, our study provides comprehensive insights into the unique genomic and transcriptomic landscape of EBV+ IFDCS. We have identified multiple genetic alterations that likely contribute to the development and progression of this malignancy. Our results suggest that targeted therapy and immune checkpoint inhibitors may hold promise as potential therapeutic approaches for patients with recurrent or disseminated EBV+ IFDCS.

Humans↗

PubMed2024

DGKH-mediated phosphatidic acid oncometabolism as a driver of self-renewal and therapy resistance in HCC.

BACKGROUND AND AIMS: HCC is characterized by metabolic pathway aberrations, which enable cancer cells to meet their energy demands and accelerate malignant progression. Identifying novel metabolic players governing therapy resistance and self-renewal in HCC is crucial, as these properties are likely responsible for tumor recurrence. APPROACH AND RESULTS: Clinical traits and RNA-seq of patients with HCC in The Cancer Genome Atlas were used for weighted gene coexpression network analysis, where 1 module was significantly correlated with advanced pathological stage and stem cell population maintenance. Further analysis of this module by integrating data obtained from HCC patient nonresponders to tyrosine kinase inhibitors identified 361 commonly deregulated genes. Intriguingly, these genes are significantly enriched in the intracellular signal transduction pathway, with diacylglycerol kinase eta (DGKH) ranked as the most enriched gene in poorly differentiated HCC tumors. Clinically, DGKH was elevated in tumor tissues compared to nontumor tissues. Patients with higher DGKH expression exhibited a more undifferentiated state and were less responsive to tyrosine kinase inhibitors. Functional assays using DGKH-manipulated HCC cell lines demonstrated that DGKH augmented aggressive features, including cancer stemness, therapy resistance, and metastasis. Upstream of DGKH , we discovered that the E1A-associated protein p300 (EP300) binds to DGKH's promoter region, thereby increasing its transcriptomic expression. Mechanistically, DGKH promotes mTOR signaling by producing phosphatidic acid. In an immunocompetent mouse model, cotreatment with sorafenib and liver-directed AAV8-mediated Dgkh depletion significantly reduced tumor burden, self-renewal, phosphatidic acid production, and mTOR signaling. CONCLUSIONS: Our research demonstrated that DGKH is a crucial oncometabolic regulator of cancer stemness and therapy resistance, suggesting that inhibiting DGKH may lead to more effective HCC treatment.

Humans↗