Ask about this productRelated genes to: SEMA6D Blocking Peptide
- Gene:
- SEMA6D NIH gene
- Name:
- semaphorin 6D
- Previous symbol:
- -
- Synonyms:
- KIAA1479, FLJ11598
- Chromosome:
- 15q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-09-17
- Date modifiied:
- 2016-01-14
Related products to: SEMA6D Blocking Peptide
Related articles to: SEMA6D Blocking Peptide
- Colorectal cancer (CRC) persists as the third most prevalent cause of cancer-associated mortality worldwide, largely due to late diagnosis, limited treatment efficacy, and poor response to immunotherapy. However, the underlying molecular mechanisms remain incompletely characterized. This study identified Semaphorin 6D (SEMA6D) as a potential tumor suppressor that was markedly underexpressed in CRC and associated with poor prognosis. Promoter hypermethylation emerges as the primary mechanism underlying its transcriptional silencing, with notably low expression observed in CIMP-H, MSI-H, CMS4 and CMS1 subtypes. Functional experiments demonstrated that SEMA6D overexpression significantly attenuated cellular proliferation, epithelial-mesenchymal transition (EMT), and migratory capacity in vitro, while concurrently suppressing tumor growth and metastatic spread in vivo. Conversely, SEMA6D depletion induced pro-tumorigenic phenotypes. Moreover, SEMA6D enhanced anti-tumor immunity by enhancing the infiltration of CD4 and CD8 T lymphocytes into the tumor microenvironment (TME). Importantly, treatment with hypomethylating agents successfully restored SEMA6D expression and potentiated immunotherapy efficacy. Mechanistically, Plexin A4 was identified as the key receptor mediating SEMA6D signaling in CRC. Plexin A4 facilitates the interaction between SEMA6D and IRF9, promoting IRF9 activation and subsequent induction of the type I interferon signaling pathway. This cascade enhances T cell-infiltration, remodels the immunosuppressive TME, and ultimately suppresses tumor progression. Collectively, our findings establish SEMA6D as a crucial tumor suppressor epigenetically silenced in CRC. SEMA6D represents a valuable indicator for molecular classification, prognostic evaluation, and clinical decision-making in CRC. The Plexin A4/SEMA6D/IRF9 axis represents a promising therapeutic target, while the demonstrated efficacy of demethylating agents provides a strong rationale for incorporating epigenetic therapies into CRC treatment strategies, offering significant translational implications for clinical practice. - Source: PubMed
Publication date: 2026/02/24
Shi WeiZhang FanSun Wei-QingLiang Li-QiKrishnan Shamalagowri - Environmental temperature significantly influences immune responses. Cold exposure suppresses host defense against infections and exacerbates autoimmune and allergic conditions. However, the molecular mechanisms underlying temperature-dependent immune regulation remain unclear. In this study, we evaluated the cold-activated sympathetic modulation of immune responses. We presented that semaphorin 6D (Sema6D), an axon guidance molecule, is required for proper sympathetic nerve distribution. While both wild-type and Sema6d-/- mice developed experimental autoimmune encephalomyelitis (EAE) similarly at room temperature (22 °C), disease progression was attenuated in Sema6d-/- mice specifically under cold exposure (10 °C). Additionally, endothelial cell-specific Sema6d-/- (Sema6dΔVEcad) mice exhibited cold-specific attenuation of EAE development. Notably, Sema6dΔVEcad mice showed increased perivascular sympathetic innervation in lymph nodes, which resulted in enhanced norepinephrine-induced tissue hypoxia and cellular stress responses, leading to attenuated T-cell responses under cold exposure. These immunosuppressive effects were restored by pharmacological ablation of the sympathetic nerves, showing that the proper sympathetic nerve distribution in lymphoid organs is critical for immune competence under cold exposure. Collectively, these findings not only indicate that Sema6D is a key axon guidance molecule for sympathetic nerve distribution but also show a potential mechanism underlying the environmentally modulated progression of autoimmune diseases. - Source: PubMed
Mizuno YumikoMatsushita HiroakiFukushima YokoKobuchi ShuheiKoyama ShoheiNishide MasayukiNakanishi YoshimitsuIzumi MayukoNaito MaikoMaruyama KazuichiOkuno TatsusadaKumanogoh Atsushi - The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. We identify two genome-wide significant loci in APOE-ε4 carriers, reaching genome-wide significance for executive function. These loci also demonstrate nominal associations across the other domains, suggesting broad effects on cognition. In non-carriers, we identify a genome-wide significant association at ITGB8 restricted to executive function, and another locus associated with language. We further link these loci to SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases. Post-GWAS analyses implicate additional genes including SLCO1A2, and DNAH11. Genetic correlation analyses reveal differences by APOE-ε4 status for immune-related traits, suggesting immune-related predispositions may exacerbate cognitive risk in APOE-ε4 carriers. - Source: PubMed
Publication date: 2026/02/20
Contreras Alex GWalters SkylarEissman Jaclyn MArcher Derek BRegelson Alexandra NDurant AlainaClifton MichelleMukherjee SubhabrataLee Michael LChoi Seo-EunScollard PhoebeTrittschuh Emily HMez JesseBush William SKunkle Brian WCruchaga CarlosNaj Adam CGifford Katherine ABilgel MuratKuzma Amanda B Cuccaro Michael LPericak-Vance Margaret AFarrer Lindsay AWang Li-SanSchellenberg Gerard DHaines Jonathan LJefferson Angela LKukull Walter AKeene C DirkSaykin Andrew JThompson Paul MMartin Eden RAlbert Marilyn SJohnson Sterling CEngelman Corinne DFerrucci LuigiBennett David ABarnes Lisa LSchneider Julie ASperling Reisa AResnick Susan MCrane Paul KDumitrescu LoganHohman Timothy J - Tobacco smoking is a major risk factor for cardiovascular and lung diseases. A better understanding of its neurobiological underpinnings will benefit the prevention of smoking-related illnesses and mortality. Previous studies link smoking to increased iron concentration in the striatum, a central component of the brain's reward system, and to reduced cognitive performance. This study aimed to investigate whether smoking and striatal iron share common biological pathways and to assess potential causal relationships between the two. - Source: PubMed
Publication date: 2026/01/31
Trofimova OlgaIuliani IlariaBergmann Sven - Osteoarthritis (OA) is a degenerative joint disease that affects over 500 million individuals globally, characterized by the degradation of cartilage, subchondral bone sclerosis, and synovitis. A key factor in the progression of OA is synovial inflammation, which is driven by macrophage polarization and inflammasome activation. This inflammation exacerbates cartilage degradation, creating a vicious cycle that accelerates disease progression. Targeting macrophage activity presents a promising therapeutic strategy to alleviate the symptoms and progression of OA. - Source: PubMed
Publication date: 2025/10/07
Zhang WenchaoLi ChongruiYao JiapeiXu ZhonghuaHuang YongLu YaojunLin XiaolongGuo ZiliZhou Xindie