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Pan-cancer analysis identifies KANSL2 as a cell-cycle-associated regulator of tumor progression and immunity in liver hepatocellular carcinoma
Clin Exp Med. 2026 Jul 26;26(1):329. doi: 10.1007/s10238-026-02264-7.
ABSTRACT
KANSL2, a core component of the NSL histone acetyltransferase complex, has been implicated in tumorigenesis. However, its pan-cancer relevance and functional role in liver hepatocellular carcinoma (LIHC) remain unclear. Multi-omics data from TCGA, GEO, and HPA were integrated to systematically evaluate KANSL2 expression, clinical significance, genomic alterations, and immune associations across cancers. Functional enrichment, immune infiltration analyses, and single-cell transcriptomics were performed. In vitro assays were conducted to validate the biological effects of KANSL2 in LIHC cells. KANSL2 is broadly upregulated across cancers and exhibits strong diagnostic performance. Elevated KANSL2 expression correlates with unfavorable prognosis, particularly in LIHC. Mechanistically, KANSL2 and its co-expressed genes are enriched in cell-cycle progression. KANSL2 expression is also closely associated with immune infiltration and immunoregulatory signaling within the tumor microenvironment, with single-cell data indicating preferential expression in proliferative T-cell subsets. Functional experiments demonstrate that KANSL2 silencing suppresses proliferation, migration, and invasion, and induces G2/M phase arrest in LIHC cells. Notably, its effects on apoptosis are limited, suggesting that KANSL2 primarily drives tumor progression through cell-cycle-dependent mechanisms. This study identifies KANSL2 as a key regulator of tumor progression and immune remodeling in LIHC. By promoting malignancy predominantly via cell-cycle control, KANSL2 represents a promising biomarker for diagnosis and prognosis, and a potential therapeutic target.
PMID:42726304 | PMC:PMC13569553 | DOI:10.1007/s10238-026-02264-7
Pan-cancer analysis identifies KANSL2 as a cell-cycle-associated regulator of tumor progression and immunity in liver hepatocellular carcinoma
Clin Exp Med. 2026 Jul 26;26(1):329. doi: 10.1007/s10238-026-02264-7.
ABSTRACT
KANSL2, a core component of the NSL histone acetyltransferase complex, has been implicated in tumorigenesis. However, its pan-cancer relevance and functional role in liver hepatocellular carcinoma (LIHC) remain unclear. Multi-omics data from TCGA, GEO, and HPA were integrated to systematically evaluate KANSL2 expression, clinical significance, genomic alterations, and immune associations across cancers. Functional enrichment, immune infiltration analyses, and single-cell transcriptomics were performed. In vitro assays were conducted to validate the biological effects of KANSL2 in LIHC cells. KANSL2 is broadly upregulated across cancers and exhibits strong diagnostic performance. Elevated KANSL2 expression correlates with unfavorable prognosis, particularly in LIHC. Mechanistically, KANSL2 and its co-expressed genes are enriched in cell-cycle progression. KANSL2 expression is also closely associated with immune infiltration and immunoregulatory signaling within the tumor microenvironment, with single-cell data indicating preferential expression in proliferative T-cell subsets. Functional experiments demonstrate that KANSL2 silencing suppresses proliferation, migration, and invasion, and induces G2/M phase arrest in LIHC cells. Notably, its effects on apoptosis are limited, suggesting that KANSL2 primarily drives tumor progression through cell-cycle-dependent mechanisms. This study identifies KANSL2 as a key regulator of tumor progression and immune remodeling in LIHC. By promoting malignancy predominantly via cell-cycle control, KANSL2 represents a promising biomarker for diagnosis and prognosis, and a potential therapeutic target.
PMID:42726304 | PMC:PMC13569553 | DOI:10.1007/s10238-026-02264-7
Harbor Adapters and Harbor-Index: Infrastructure and a Curated Meta-Dataset for Large-Scale Agentic Evaluation
Synergistic Vision-Language Reinforcement Enables Scalable On-Demand Analysis across Diverse Clinical Tasks
Instance-Aware Algorithm Selection for Maximum Clique via a Dual-Channel Graph Neural Architecture
City Editing: Hierarchical Agentic Execution for Dependency-Aware Urban Geospatial Modification
A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.
ABSTRACT
Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.
PMID:42189071 | DOI:10.1002/advs.75839
A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.
ABSTRACT
Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.
PMID:42189071 | DOI:10.1002/advs.75839
Extracting Training Data from Diffusion Language Models via Infilling
Explainable Retinal Imaging for Prediction of Multi-Organ Dysfunction in Type 2 Diabetes
Explainable Multi-Task Retinal Imaging Reveals Microvascular Signals for Systemic Risk Stratification in Type 2 Diabetes: A Pilot Study
Simulating Human Memory with Language Models
Agent Primitives: Reusable Latent Building Blocks for Multi-Agent Systems
Contextual Rollout Bandits for Reinforcement Learning with Verifiable Rewards
Fetal monitoring for high-risk pregnancies using a wearable ultrasound patch
Nature Biotechnology, Published online: 26 May 2026; doi:10.1038/s41587-026-03140-1
A wearable ultrasound device is optimized for continuous monitoring of pregnancies.Multi-omics Analysis Reveals the Protection of a Quadruple Probiotic Mixture in Experimental Autoimmune Hepatitis
Probiotics Antimicrob Proteins. 2026 May 23. doi: 10.1007/s12602-026-11062-2. Online ahead of print.
ABSTRACT
Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease with a rising global incidence. The treatment of AIH remains challenging because first-line drugs show limited efficacy and systemic side effects. Gut microbiota plays a crucial role in the pathogenesis of AIH, leading to growing interest in developing probiotic-based therapies. In this study, we used multi-omics analysis to investigate the therapeutic effects of a quadruple probiotic mixture (Probiotic-quad) consisting of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus in a well-established chronic AIH murine model. Our results showed that Probiotic-quad treatment significantly alleviated AIH progression, as evidenced by lower serum liver enzyme levels, ameliorated hepatic inflammatory infiltration and histopathological damage. Metagenomic sequencing results showed that gut dysbiosis in AIH mice was partially reversed after Probiotic-quad administration. Additionally, the integrity of the intestinal epithelial barrier was restored, accompanied by a reduction in serum lipopolysaccharide levels. Untargeted metabolomic and transcriptomic analysis revealed that Probiotic-quad treatment was linked to alterations in hepatic metabolism, including the citrate cycle and tryptophan metabolism, and was associated with reduced activation of the NF-κB and NOD-like receptor signaling pathways. These findings suggest that Probiotic-quad treatment ameliorates AIH severity and is potentially associated with changes in hepatic immune responses, metabolism, gut microbiota, and intestinal barrier function, highlighting its potential as an adjuvant therapy for AIH.
PMID:42176246 | DOI:10.1007/s12602-026-11062-2
Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applications
Cell Death Discovery, Published online: 23 May 2026; doi:10.1038/s41420-026-03147-2
Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applicationsRepresentation learning to advance multi-institutional studies with electronic health record data from US and France
SETDB2 induces abnormal SHP-1 splicing and promotes immunosuppression in hepatocellular carcinoma
Oncogene, Published online: 07 April 2026; doi:10.1038/s41388-026-03759-z
SETDB2 induces abnormal SHP-1 splicing and promotes immunosuppression in hepatocellular carcinoma