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AutoSG: LLM-Driven Solver Generation Solely from Task Prompts for Expensive Optimization
HiTeC: Hierarchical Contrastive Learning on Text-Attributed Hypergraph with Semantic-Aware Augmentation
HiGraph: A Large-Scale Hierarchical Graph Dataset for Malware Analysis
SNHG12 drives gastric cancer progression by activating the Wnt/beta-catenin-mediated serine synthesis pathway
J Transl Med. 2026 Apr 30;24(1):638. doi: 10.1186/s12967-026-08173-3.
ABSTRACT
BACKGROUND: Metabolic reprogramming is a hallmark of gastric cancer and is essential for sustaining rapid proliferation and malignant progression. The serine synthesis pathway (SSP), a key branch of glycolysis coupled to one-carbon metabolism (OCM), plays a central role in nucleotide biosynthesis, redox homeostasis, and epigenetic regulation. Although aberrant SSP activation has been implicated in gastric cancer, its upstream regulatory mechanisms remain poorly defined. Long non-coding RNAs (lncRNAs) have emerged as critical modulators of oncogenic signaling and metabolism. This study aimed to elucidate the role of the lncRNA SNHG12 in gastric cancer progression and to determine whether it drives metabolic reprogramming through the Wnt/β-catenin-SSP axis.
METHODS: SNHG12 expression and clinical relevance were analyzed using public datasets, clinical gastric cancer specimens, and cell lines. Gain- and loss-of-function experiments were performed to assess the effects of SNHG12 on proliferation, apoptosis, migration, and invasion. Transcriptomic profiling, targeted metabolomics, and integrative multi-omics analyses were used to characterize metabolic alterations. Pharmacological inhibition of SSP (NCT503) and Wnt/β-catenin signaling (IWR-1) was applied in vitro and in vivo. A subcutaneous xenograft mouse model was used to validate tumor-promoting effects and therapeutic responses.
RESULTS: SNHG12 was significantly upregulated in gastric cancer tissues and cell lines and was associated with poor overall and progression-free survival. Functionally, SNHG12 promoted gastric cancer cell proliferation, migration, and invasion while suppressing apoptosis. Transcriptomic and targeted metabolomic analyses revealed broad metabolic alterations associated with SNHG12, including changes in serine/one-carbon metabolism, purine biosynthesis, and glutathione-related pathways. Mechanistically, SNHG12 increased Wnt/β-catenin reporter activity, promoted β-catenin nuclear accumulation, and was accompanied by increased expression of key SSP-associated enzymes, including PHGDH, PSAT1, and SHMT2. Pharmacological inhibition of SSP or Wnt/β-catenin signaling partially reversed SNHG12-induced malignant phenotypes in vitro and suppressed tumor growth in xenograft models.
CONCLUSIONS: This study identifies SNHG12 as an important regulator of metabolic reprogramming in gastric cancer. Our data support a model in which SNHG12 promotes gastric cancer cell proliferation, invasion, and migration through SSP regulation, and suggest that its effects on the SSP may be mediated, at least in part, through modulation of SSP-associated enzymes via the Wnt/β-catenin pathway. These findings support SNHG12 as a candidate biomarker and a potential therapeutic target for combined metabolic and signaling-based interventions in gastric cancer.
PMID:42063161 | PMC:PMC13151230 | DOI:10.1186/s12967-026-08173-3
Empirical Characterization of Rationale Stability Under Controlled Perturbations for Explainable Pattern Recognition
VLBiasBench: A Comprehensive Benchmark for Evaluating Bias in Large Vision-Language Model
Mind Your HEARTBEAT! Claw Background Execution Inherently Enables Silent Memory Pollution
Editing strigolactone hormone receptor for robust antiviral silencing in rice
Grokking From Abstraction to Intelligence
Spontaneous Functional Differentiation in Large Language Models: A Brain-Like Intelligence Economy
ATP-Bench: Towards Agentic Tool Planning for MLLM Interleaved Generation
LLM-Meta-SR: In-Context Learning for Evolving Selection Operators in Symbolic Regression
Accelerating Diffusion Large Language Models with SlowFast Sampling: The Three Golden Principles
Integrated transcriptomic and proteomic analyses elucidate the stress tolerance network of <em>Saccharomyces boulardii</em> under gastrointestinal challenge
Food Funct. 2026 Mar 31. doi: 10.1039/d5fo04958j. Online ahead of print.
ABSTRACT
The probiotic yeast Saccharomyces boulardii is renowned for its clinical efficacy, which is intrinsically linked to its exceptional ability to survive the harsh gastrointestinal (GI) environment. However, a comprehensive understanding of the molecular mechanisms and regulatory pathways underlying the stress tolerance of S. boulardii remains limited. This study employed an integrated transcriptomic and proteomic approach to systematically map the dynamic responses of S. boulardii to simulated GI transit. Our analysis revealed that the intestinal phase posed a significantly greater challenge than the gastric phase, triggering extensive molecular reprogramming. A core adaptive strategy was the marked upregulation of the central carbon metabolism, particularly glycolysis, as evidenced by the concerted overexpression of key enzymes at both transcriptional and translational levels, indicating a heightened demand for energy to fuel stress defence mechanisms. Furthermore, significant enrichment was observed in the pathways related to nitrogen and fatty acid metabolism. Integration of the multi-omics datasets highlighted the complexity of the regulatory response, with frequent discordance between mRNA and protein abundance underscoring the importance of post-transcriptional regulation. This study provides a detailed molecular profile of the stress tolerance network in S. boulardii, elucidating the strategic metabolic rewiring and multi-layered regulation that underpin its probiotic resilience. The findings offer valuable insights and a foundational resource for the future development of enhanced probiotic therapies.
PMID:41914832 | DOI:10.1039/d5fo04958j
Integrated transcriptomic and proteomic analyses elucidate the stress tolerance network of <em>Saccharomyces boulardii</em> under gastrointestinal challenge
Food Funct. 2026 Mar 31. doi: 10.1039/d5fo04958j. Online ahead of print.
ABSTRACT
The probiotic yeast Saccharomyces boulardii is renowned for its clinical efficacy, which is intrinsically linked to its exceptional ability to survive the harsh gastrointestinal (GI) environment. However, a comprehensive understanding of the molecular mechanisms and regulatory pathways underlying the stress tolerance of S. boulardii remains limited. This study employed an integrated transcriptomic and proteomic approach to systematically map the dynamic responses of S. boulardii to simulated GI transit. Our analysis revealed that the intestinal phase posed a significantly greater challenge than the gastric phase, triggering extensive molecular reprogramming. A core adaptive strategy was the marked upregulation of the central carbon metabolism, particularly glycolysis, as evidenced by the concerted overexpression of key enzymes at both transcriptional and translational levels, indicating a heightened demand for energy to fuel stress defence mechanisms. Furthermore, significant enrichment was observed in the pathways related to nitrogen and fatty acid metabolism. Integration of the multi-omics datasets highlighted the complexity of the regulatory response, with frequent discordance between mRNA and protein abundance underscoring the importance of post-transcriptional regulation. This study provides a detailed molecular profile of the stress tolerance network in S. boulardii, elucidating the strategic metabolic rewiring and multi-layered regulation that underpin its probiotic resilience. The findings offer valuable insights and a foundational resource for the future development of enhanced probiotic therapies.
PMID:41914832 | DOI:10.1039/d5fo04958j
Toward Faithful Segmentation Attribution via Benchmarking and Dual-Evidence Fusion
Mind Your HEARTBEAT! Claw Background Execution Inherently Enables Silent Memory Pollution
Generalizable Heuristic Generation Through LLMs with Meta-Optimization
Protein phosphatase 2A methylation state impacts α-synucleinopathy in mouse models
Cell Death Discovery, Published online: 24 March 2026; doi:10.1038/s41420-026-03045-7
Protein phosphatase 2A methylation state impacts α-synucleinopathy in mouse models