Biology subjects

Hong, S. Y.

Publications and source records attributed to Hong, S. Y..

3 recordsLinked to original sources

bioRxiv2026

Spatial Transcriptomics Reveals a Conserved Border Niche and Etiology-Associated Immune Rewiring in Hepatocellular Carcinoma

Background and AimsThe tumor-stroma interface in hepatocellular carcinoma (HCC) harbors critical intercellular interactions that shape immune evasion and treatment response, yet its spatial architecture remains poorly characterized across etiologies. Whether hepatitis B virus (HBV)-related and non-B non-C (NBNC) HCC share conserved border niche features or exhibit etiology-specific microenvironment programs is unknown. We aimed to spatially resolve the tumor boundary ecosystem and identify etiology-associated signaling networks with translational relevance. Approach and ResultsWe performed 10x Visium spatial transcriptomics on 11 HCC specimens (7 HBV, 4 NBNC) and applied a machine-learning pipeline integrating CancerFinder and SpaceFlow to define tumor, boundary, and stromal domains. Across etiologies, the boundary zone showed a recurrent desmoplastic niche characterized by cancer-associated fibroblast, tumor-associated macrophage, and tumor endothelial cell accumulation with collagen-integrin extracellular matrix remodeling, including COL1A1-ITGA11 and COL4A1-ITGAV. Etiology-associated differences were observed in the organization of border-zone signaling programs. In representative HBV-related sections, CCL19-CCR7 signaling showed a comparatively restricted, endothelial-skewed topology, whereas representative NBNC sections showed broader inflammatory ligand-receptor networks with elevated NF-kB-associated pathway activity. ConclusionsThe HCC tumor-stroma border harbors a recurrent desmoplastic niche upon which etiology-associated immune regulatory programs may be superimposed. These findings generate spatial hypotheses relevant to etiology-informed biomarker development and future therapeutic stratification.

cancer biology↗

bioRxiv2025

Rapaprotin is Activated by an Endopeptidase to Disassemble 26S Proteasome

The 19S regulatory particle (RP) associates with the 20S core particle (CP) to form the 26S proteasome, an evolutionarily conserved holoenzyme that plays key roles in both physiological and pathological processes. Proteasome inhibitors that target the catalytic subunits within the 20S have proven to be valuable research tools and therapeutics for various cancers. Herein we report the discovery of rapaprotin, a 26S proteasome assembly inhibitor from our natural product-inspired hybrid macrocycle rapafucin library. Rapaprotin induces apoptosis in both myeloma and leukemia cell lines. Genome-wide CRISPR-Cas9 screen identified a cytosolic enzyme, prolyl endopeptidase (PREP) that is required for the pro-apoptotic activity of rapaprotin. Further mechanistic studies revealed that rapaprotin acts as a molecular transformer, changing from an inactive cyclic form into an active linear form, rapaprotin-L, upon PREP cleavage, to block 26S proteasome activity. Time-resolved cryogenic electron microscopy (cryo-EM) revealed that rapaprotin-L induces dissociation of the 19S RP from the 26S holoenzyme, which was verified in cells. Furthermore, rapaprotin exhibits a marked synergistic effect with FDA-approved proteasome inhibitors and resensitizes drug-resistant multiple myeloma cells from patients to bortezomib. Taken together, these results suggest that rapaprotin is a new chemical tool to probe the dynamics of the 26S proteasome assembly and a promising anticancer drug lead.

pharmacology and toxicology↗

bioRxiv2024

Chromosome-level genome assembly of milk thistle (Silybum marianum (L.) Gaertn.)

Silybum marianum (L.) Gaertn., commonly known as milk thistle, is a medicinal plant belonging to the Asteraceae family. This plant has been recognized for its medicinal properties for over 2,000 years. However, the genome of this plant remains largely undiscovered, having no reference genome at a chromosomal level. Here, we assembled the chromosome-level genome of S. marianum, allowing for the annotation of 53,552 genes and the identification of transposable elements comprising 58% of the genome. The genome assembly from this study showed 99.1% completeness as determined by BUSCO assessment, while the previous assembly (ASM154182v1) showed 36.7%. Functional annotation of the predicted genes showed 50,329 genes (94% of total genes) with known protein functions in public databases. Comparative genome analysis among Asteraceae plants revealed a striking conservation of collinearity between S. marianum and C. cardunculus . The genomic information generated from this study will be a valuable resource for milk thistle breeding and for use by the larger research community.

genomics↗