Biomedical subjects

Jie Xiong

Publications and source records attributed to Jie Xiong.

4 recordsLinked to original sources

PubMed2026

The N6-methyladenosine reader IGF2BP2 in T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) represents a highly heterogeneous and aggressive lymphoid neoplasm that lacks pathogenic biomarkers of RNA modification with therapeutic potential. IGF2BP2 is recognized as an N6-methyladenosine reader critically involved in oncogenesis. In this study, we observed consistently high expression of IGF2BP2 across common nodal PTCL subtypes in 3 independent external cohorts, which was further confirmed in our RNA-sequencing (RNA-seq) data set of 196 patients with newly diagnosed PTCL. Both in vitro and in vivo, IGF2BP2 promoted tumor cell growth and inhibited CD8+ T-cell infiltration within the tumor microenvironment. Mechanistically, IGF2BP2 bound to endosome-related genes (RAB4, VPS35, RAB9, and STAM) to maintain their stability, which resulted in enhanced endocytic activity and increased internalization of membrane proteins, and ultimately induced tumor cell proliferation and inhibition of CD8+ T-cell-mediated tumor cytotoxicity. The relationship between IGF2BP2 and endocytosis-associated genes was confirmed using RNA-seq data from patients with PTCL. IGF2BP2 as an upstream regulator of both tumor growth and immune suppression was further demonstrated in patient-derived xenograft models and a coculture system established using tumor samples from patients with PTCL and peripheral blood mononuclear cells. Notably, therapeutic targeting of IGF2BP2 with CWI1-2 suppressed endocytosis and impeded tumor growth in both cell lines and patient-derived xenograft models. Collectively, our findings highlight IGF2BP2 as a clinically relevant oncogenic driver in PTCL that integrates tumor-intrinsic growth signals with immune evasion through endocytosis-centered regulation, providing a novel therapeutic rationale for RNA modification-based strategies that concurrently target tumor cells and the tumor microenvironment.

Humans↗

PubMed2026

Screening of molecular biomarkers ASPN and LBH and construction of a prediction nomogram for the progression of esophagogastric junction adenocarcinoma.

BACKGROUND: Esophagogastric junction adenocarcinoma (EGJA) is an aggressive malignancy of the digestive system with poor prognosis. Early diagnosis and accurate prediction of tumor progression remain major clinical challenges. This study aimed to identify and validate molecular biomarkers and construct a precise diagnostic model, providing a scientific basis for individualized treatment. METHODS: Differentially expressed genes (DEGs) associated with EGJA were identified using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed for further screening. The protein expression levels of ASPN and LBH were validated by immunohistochemistry in both tumor and adjacent non-tumor tissues. A nomogram was constructed by integrating clinical and pathological features, and its performance and clinical utility were assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: Immunohistochemistry demonstrated that the protein expression of ASPN was significantly upregulated in tumor tissues, with expression levels increasing with tumor stage. Conversely, LBH was downregulated in tumor tissues and decreased with advancing stages. The predictive model achieved an area under the curve (AUC) value of 0.977, indicating excellent diagnostic and prognostic performance. DCA confirmed the clinical net benefit of the model. CONCLUSIONS: ASPN and LBH are critical molecular biomarkers for EGJA. The nomogram combining these two markers enables accurate distinction between early and advanced-stage tumors, offering significant support for early diagnosis of EGJA.

ASPN↗

PubMed2025

Multi-omic underpinnings of heterogeneous aging across multiple organ systems.

Aging is the main determinant of chronic diseases and mortality, yet organ-specific aging trajectories vary, and the molecular basis underlying this heterogeneity remains unclear. To elucidate this, we integrated genomic, epigenomic, transcriptomic, proteomic, and metabolomic data, employing post-genome-wide association study methodologies to systematically investigate the molecular mechanisms of nine organ-specific aging clocks and four blood-based epigenetic clocks. We uncovered genetic correlations and specific phenotypic clusters among these aging-related traits, identified prioritized genetic drug targets for heterogeneous aging, and elucidated downstream proteomic and metabolomic effects mediated by heterogeneous aging. We constructed a cross-layer molecular interaction network of heterogeneous aging across multiple organ systems and characterized detectable biomarkers of this heterogeneity. Integrating these findings, we developed an R/Shiny-based framework that provides a comprehensive multi-omic molecular landscape of heterogeneous aging, thereby advancing the understanding of aging heterogeneity and informing precision medicine strategies to delay organ-specific aging and prevent or treat its associated chronic diseases.

Aging↗

PubMed2024

Targeting the transcription factor YY1 is synthetic lethal with loss of the histone demethylase KDM5C.

An understanding of the enzymatic and scaffolding functions of epigenetic modifiers is important for the development of epigenetic therapies for cancer. The H3K4me2/3 histone demethylase KDM5C has been shown to regulate transcription. The diverse roles of KDM5C are likely determined by its interacting partners, which are still largely unknown. In this study, we screen for KDM5C-binding proteins and show that YY1 interacts with KDM5C. A synergistic antitumor effect is exerted when both KDM5C and YY1 are depleted, and targeting YY1 appears to be a vulnerability in KDM5C-deficient cancer cells. Mechanistically, KDM5C promotes global YY1 chromatin recruitment, especially at promoters. Moreover, an intact KDM5C JmjC domain but not KDM5C histone demethylase activity is required for KDM5C-mediated YY1 chromatin binding. Transcriptional profiling reveals that dual inhibition of KDM5C and YY1 increases transcriptional repression of cell cycle- and apoptosis-related genes. In summary, our work demonstrates a synthetic lethal interaction between YY1 and KDM5C and suggests combination therapies for cancer treatments.

YY1 Transcription Factor↗