Ask about this productRelated genes to: LRG1 Blocking Peptide
- Gene:
- LRG1 NIH gene
- Name:
- leucine rich alpha-2-glycoprotein 1
- Previous symbol:
- -
- Synonyms:
- LRG
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-12
- Date modifiied:
- 2016-06-06
Related products to: LRG1 Blocking Peptide
Related articles to: LRG1 Blocking Peptide
- Breast carcinoma is a major cause of cancer-related mortality among women worldwide. Identifying novel molecular targets remains essential, particularly for aggressive triple-negative breast cancer (TNBC). Leucine-rich alpha-2-glycoprotein 1 (LRG1) has been linked to tumor progression and angiogenesis, but its molecular mechanisms in breast cancer are poorly defined. We evaluated the effects of recombinant human LRG1 (rhLRG1) on cell viability and migration in MDA-MB-231 TNBC cells and performed transcriptomic profiling followed by functional enrichment analyses using GenArise, Cytoscape, and R-based tools. RhLRG1 treatment significantly increased cell viability and migration. Transcriptomic analysis revealed activation of key oncogenic cascades, including the PI3K/AKT, MAPK, and RAS signaling pathways. Hub-gene analysis identified upregulated genes involved in proliferation (, , ), angiogenesis (, ), and apoptosis (, ), whereas downregulated genes were associated with apoptotic resistance (, ) and adhesion (, ). Functional enrichment highlighted LRG1's role in the bioinformatic analysis of differentially expressed genes that were obtained from microarray assays. LRG1 remodels the tumor microenvironment by promoting proliferation, angiogenesis, and apoptotic sensitivity while repressing resistance-related genes. These findings position LRG1 as a potential diagnostic biomarker and therapeutic target for advanced breast carcinoma. - Source: PubMed
Publication date: 2026/04/18
Osorio-Antonio FedericoDiaz-González Daniela MichelCampos-Viguri Gabriela ElizabethSánchez-López José ManuelCortez-Sánchez José LuisCastelán FranciscoChávez-Rios Jesús RamsesMaycotte-González PaolaCortés-Hernández PaulinaPeralta-Zaragoza OscarBautista-Rodríguez Elizabeth - Neutrophil extracellular traps are implicated in immunothrombosis and neuroinflammation in ischemic stroke, but blood-based markers that distinguish subtype-specific thromboinflammatory patterns remain limited. We applied an integrated multi-omics strategy combining multi-cohort peripheral-blood transcriptomics, machine-learning feature selection, Mendelian randomization, and single-cell RNA sequencing, followed by in silico perturbation analyses and compound prioritization with molecular docking, molecular dynamics simulation, and cellular thermal shift assays. Plasma citrullinated histone H3 levels were elevated across ischemic stroke subtypes and were highest in cardioembolic stroke. Integrative transcriptomic analysis identified a 7-gene neutrophil extracellular trap-related diagnostic signature comprising PADI4, C5AR1, MMP9, LRG1, NFIL3, TREM1, and PGLYRP1, with good cross-cohort diagnostic performance (area under the curve 0.789-0.834). Among these genes, MMP9 showed a broad association across ischemic stroke cohorts, whereas PGLYRP1 showed a cardioembolic stroke-enriched signal and a putative causal association with cardioembolic stroke in Mendelian randomization analyses. Two-step mediation analyses did not support a significant mediating role for the tested systemic cytokines, consistent with a more localized thromboinflammatory context. Single-cell computational perturbation suggested that Pglyrp1 may influence neutrophil-associated programs and intercellular communication. Molecular dynamics simulations prioritized Naringin as a candidate MMP9-binding compound, and cellular thermal shift assays supported cellular target engagement for the MMP9-Naringin pair. These findings provide a neutrophil extracellular trap-centered framework for biologically informed stratification of ischemic stroke and nominate MMP9 and PGLYRP1 as candidate biomarkers and therapeutic hypotheses for further validation. - Source: PubMed
Publication date: 2026/04/30
Tan HaozhouGong HaoyuLi HuiHuang MengyaoZhang JingyuanLiu YanLi YingSong YuanjianFeng Qian - Leucine-rich α-2-glycoprotein 1 (LRG1) is markedly upregulated in colorectal cancer (CRC) and correlates with a poor prognosis, yet its role in drug response remains unclear. Here, we identify an association between LRG1 and thymidylate synthase (TYMS) that influences 5-fluorouracil (5-FU) sensitivity in CRC. LRG1 silencing is associated with reduced TYMS expression and enhanced 5-FU cytotoxicity, an effect partially mediated through the PI3K-AKT-mTOR signaling pathway. Guided by these observations, we constructed a lysosome-targeting liposomal nanochimera (Lipo-EM@5-FU) that integrates targeted degradation of LRG1 with 5-FU chemotherapy to achieve coordinated modulation of signaling and metabolic processes. Upon uptake, lysosomal degradation of LRG1 is associated with attenuation of PI3K-AKT-mTOR signaling and reduced TYMS expression, while 5-FU further blocks its enzymatic activity, contributing to cell cycle arrest and apoptosis. In tumor-bearing mice, Lipo-EM@5-FU achieves prolonged circulation, enhanced tumor accumulation, and potent antitumor efficacy with minimal systemic toxicity. This work reveals a functional link between LRG1 and 5-FU responsiveness, establishing a degradation-driven chemosensitization paradigm for colorectal cancer therapy. - Source: PubMed
Publication date: 2026/04/28
Wu GangZhang KejuanMin HuanDu LinLi JunyaoLi WenzhengZhang YinlongDu ShengnanQi YingqiuZhang Wei - Neuroinflammation and pyroptosis driven by excessive microglial activation play key roles in cerebral ischemia-reperfusion injury (CIRI). Hyperbaric oxygen preconditioning (HBO-PC) exhibits neuroprotective effects, but its mechanisms remain unclear. Leucine-rich α-2-glycoprotein 1 (LRG1) is implicated in CIRI pathology, yet whether HBO-PC modulates neuroinflammation and pyroptosis via LRG1 is unknown. - Source: PubMed
Lv WenyingLv JunzheXiong KexinYuan ShunshunYang JingyaoGuo Dazhi - Endothelial barrier dysfunction and consequent vascular injury are central contributors to acute lung injury (ALI) during sepsis. However, the underlying mechanisms remain incompletely understood, and effective therapeutic strategies targeting endothelial repair are still lacking. Here, we identify that intracellular leucine-rich α2-glycoprotein 1 (LRG1) in endothelial cells (EC) is significantly upregulated and directly promotes the degradation of vascular endothelial cadherin (VE-cadherin), a core adherens junction protein essential for maintaining vascular barrier integrity in septic ALI. Mechanistically, LRG1 recruits the E3 ubiquitin ligase membrane-associated ring-CH-type finger 2 (MARCH2) to catalyze K48-linked polyubiquitination of VE-cadherin at lysine 633, leading to its proteasomal degradation and subsequent endothelial barrier disruption. Genetic deletion of Lrg1 or pharmacological intervention with a proteolysis targeting chimera (PROTAC)-based degradation strategy significantly reduced VE-cadherin loss, alleviated endothelial hyperpermeability, and mitigated ALI in septic mice. Collectively, our study elucidates a previously unrecognized role of endothelial LRG1 in disrupting EC adherens junctions, providing novel insights into the pathogenesis of sepsis-associated injury and proposing a potential therapeutic strategy for sepsis-induced ALI and acute respiratory distress syndrome (ARDS). - Source: PubMed
Publication date: 2026/04/27
Fang Xiao-WeiFu Jia-JiZhang Yi-RenZhao YueQiu YangZhou XiZhang Ding-YuXu Ji-QianShang You