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The Menu Is an Execution Prior: State-Path Tool Menus for Online Agents
Integrative Pan-Cancer Characterization of lncRNA UPK1A-AS1 and Its Role in Hypoxia-Associated Sorafenib Resistance in Hepatocellular Carcinoma
Anal Cell Pathol (Amst). 2026;2026(1):e1554526. doi: 10.1155/ancp/1554526.
ABSTRACT
Long noncoding RNAs (lncRNAs) are emerging as critical regulators of tumor initiation and progression through transcriptional and posttranscriptional mechanisms. UPK1A antisense RNA 1 (UPK1A-AS1), a cancer-associated lncRNA, has been reported to participate in oncogenic processes; however, its overall landscape across human malignancies and its biological role in therapy resistance remain poorly understood. Given the increasing importance of identifying functional lncRNAs with prognostic and therapeutic potential, this study presents a comprehensive multiomics characterization of UPK1A-AS1 and its experimental validation in hepatocellular carcinoma (HCC). We integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), the cancer immunology data engine (CIDE), and the cBioPortal for cancer genomics (cBioPortal) to systematically assess its expression pattern, genomic alterations, clinical significance, and immunological associations. Our analyses revealed that UPK1A-AS1 is significantly upregulated in multiple tumor types, with copy-number amplification as the predominant genomic alteration driving its overexpression. Elevated UPK1A-AS1 expression was correlated with advanced disease stage, poor differentiation, immune exclusion, and unfavorable prognosis, supporting its potential as a cancer type-dependent biomarker. In parallel, functional studies demonstrated that hypoxia transcriptionally induces UPK1A-AS1 in HCC, where it promotes sorafenib resistance by suppressing apoptosis. Silencing UPK1A-AS1 restored apoptotic and enhanced sorafenib efficacy both in vitro and in vivo. Collectively, our findings suggest that UPK1A-AS1 is a hypoxia-inducible oncogenic lncRNA that plays dual roles in cancer, with cancer type-dependent associations with progression and immune modulation across malignancies and mechanistically mediating hypoxia-associated drug resistance in HCC.
PMID:42678131 | PMC:PMC13532061 | DOI:10.1155/ancp/1554526
AI-enhanced adaptive virtual screening of large libraries for ligand discovery
Nature Biotechnology, Published online: 01 September 2026; doi:10.1038/s41587-026-03217-x
Massive chemical libraries are screened computationally at scale.Benchmarking the Limits of In-Context Reinforcement Learning for Ad-Hoc Teamwork
Test-Time Deep Thinking to Explore Implicit Rules
FrontierOR: Benchmarking LLMs' Capacity for Efficient Algorithm Design in Large-Scale Optimization
DRScaffold: Boosting Dense-Scene Reasoning in Lightweight Vision Language Models
NDRG2 orchestrates circadian clock stability to suppress tumorigenesis and potentiate oxaliplatin response in colorectal cancer
Oncogene, Published online: 19 May 2026; doi:10.1038/s41388-026-03823-8
NDRG2 orchestrates circadian clock stability to suppress tumorigenesis and potentiate oxaliplatin response in colorectal cancerCharacterization of dysbiosis patterns in gut microbiota of digestive system cancers: an umbrella review
Front Microbiol. 2026 Apr 28;17:1782471. doi: 10.3389/fmicb.2026.1782471. eCollection 2026.
ABSTRACT
Digestive system cancers (DSCs) represent a substantial global health burden. In recent years, the role of gut microbiota in the DSCs has garnered considerable attention, but its change pattern during tumor progression and the specific mechanisms are still not fully understood. We conducted a comprehensive systematic review to characterize patterns of gut microbiota dysbiosis across different DSC types and assess their clinical significance. We systematically searched four English and three Chinese databases up to January 2025 to identify systematic reviews focused on the dynamic characteristics of the gut microbiota during gastrointestinal tumorigenesis. Microbiota biodiversity and taxonomic composition were extracted to identify specific signatures associated with DSCs. The ROBIS tool was used to evaluate the methodological quality of the included studies. Ultimately, 59 studies involving six distinct DSC types were included. Data synthesis and comparison revealed distinct microbiota profiles across DSCs. At the phylum level, Bacillota was decreased in esophageal cancer (EC) and pancreatic ductal adenocarcinoma (PDAC), Pseudomonadota was augmented in EC but exhibited divergent trajectories in colorectal cancer (CRC) and PDAC. Genus-level analyses revealed Veillonella enrichment in EC and PDAC, and Fusobacterium outgrowth in EC, gastric cancer (GC) and CRC. Parvimonas and Streptococcus showed a concordant ascending trend in GC and CRC. Prevotella was overrepresented in EC and GC. This synthesis delineates a qualitative landscape of gut microbiota imbalances associated with various DSCs, highlighting the potential for these microbial shifts to serve as markers for early detection and targeted therapy. Multiomics integration and prospective cohort studies should be prioritized to accelerate clinical translation.
PMID:42131199 | PMC:PMC13161176 | DOI:10.3389/fmicb.2026.1782471
NEMESIS: Noise-suppressed Efficient MAE with Enhanced Superpatch Integration Strategy
NeoNet: An End-to-End 3D MRI-Based Deep Learning Framework for Non-Invasive Prediction of Perineural Invasion via Generation-Driven Classification
Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10304-1
Long-range interactions mediated by protein electric dipole moments have a role in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling.