SLC7A5 Pre-design Chimera RNAi
- Known as:
- SLC7A5 Pre-design Chimera RNAi
- Catalog number:
- H00008140-R01
- Product Quantity:
- 20 nmol
- Category:
- -
- Supplier:
- Abno
- Gene target:
- SLC7A5 Pre-design Chimera RNAi
Related genes to: SLC7A5 Pre-design Chimera RNAi
- Gene:
- SLC7A5 NIH gene
- Name:
- solute carrier family 7 member 5
- Previous symbol:
- -
- Synonyms:
- LAT1, E16, D16S469E, MPE16, CD98
- Chromosome:
- 16q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-28
- Date modifiied:
- 2016-10-05
Related products to: SLC7A5 Pre-design Chimera RNAi
Related articles to: SLC7A5 Pre-design Chimera RNAi
- Purpose Left ventricular hypertrophy (LVH) is a major complication of chronic hypertension and an independent cardiovascular risk factor. No clinically validated markers exist to identify hypertensive individuals at risk for developing LVH. We previously described metabolic changes preceding LVH in hypertensive rat hearts, including alterations in branched-chain amino acid (BCAA) metabolism. This study investigated whether impaired cardiac leucine uptake, measured with dynamic 5-[ F]fluoroleucine ([ F]FLE) PET imaging, could serve as marker for hypertension-induced LVH development. Procedures: [ F]FLE was synthesized following established radiochemistry protocols and dynamic [ F]FLE-PET/CT imaging was performed in 3-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) control rats (n = 4/group). Cardiac MR (CMR) imaging enabled structural co-registration. A dual-output reversible two-tissue compartment model with spill-over and partial volume corrections quantified the first-pass rate constant (K ) and total distribution volume (V ). L-type amino acid transporter 1 (LAT1/SLC7A5) protein expression and branched-chain keto acid dehydrogenase (BCKDH) phosphorylation status were assessed by immunoblotting of heart tissue. Results SHR demonstrated markedly lower K and V compared with WKY rats, consistent with reduced cardiac leucine uptake. Simultaneously, LAT1 expression was significantly reduced in SHR hearts. Elevated BCKDH phosphorylation at Ser293 suggested impaired BCAA catabolism. Conclusions Dynamic cardiac [ F]FLE-PET detects decreased leucine uptake in hypertensive rat hearts at 3 months of age, before LVH is established at 5 months. Impaired cardiac leucine uptake may thus serve as an early cardiometabolic biomarker to identify hypertensive patients at risk for LVH progression. - Source: PubMed
Publication date: 2026/06/18
Terrell WilliamLi JieKommi Damodara NBurt MeganJansen Maurits AKhanapur ShivashankarKeller Susanna RKundu Bijoy - Brain microvascular endothelial cells (BMECs) form the blood-brain barrier (BBB), a highly selective interface that restricts paracellular diffusion and regulates the transport of nutrients and drugs into the central nervous system via specialized transporters and receptors. Tight junction-associated protein 1 (Tjap1), also termed protein incorporated later into tight junctions (Pilt), has been localized to tight junctions (TJs) in epithelial cells and to the trans-Golgi network in fibroblasts; however, its expression, subcellular localization, and functional significance in BMECs are still unknown. We characterized Tjap1 subcellular localization in mouse and human BMEC cell lines as well as primary mouse BMECs by immunofluorescence with and without pharmacological Golgi disruption by treatment with Brefeldin A, Golgicide A or Pitstop 2. CRISPR/Cas9-mediated Tjap1 knockout cells were generated and examined with regard to their Golgi morphology using immunostaining. Tjap1 mRNA localization was examined by RNAscope in situ hybridization. Quantitative real-time PCR and Western blot was performed to assess the expression of BBB-associated efflux transporters, solute carrier transporters, and cellular receptors in control and Tjap1 knockout cells. Tjap1 predominantly localized to the cis-Golgi compartment, co-localizing with Gm130 rather than Tgn38, and was absent from TJs in BMECs. Tjap1 knockout induced pronounced Golgi fragmentation BMECs. Importantly, Tjap1 knockout significantly downregulated mRNA-expression of Abcb1a, Abcb1b, Abcc4, Slc2a1, Slc7a1, Slc7a5 and Tfrc, while Abcg2 was upregulated. At the protein level, a decrease in the protein levels of Abcb1, Abcc4, Slc2a1, Slc7a1, and Tfrc was observed in Tjap1 knockout cEND cells. In BMECs, Tjap1 is a cis-Golgi-associated protein required for the structural integrity of the Golgi apparatus. Its deletion is associated with Golgi fragmentation and significant alterations in the mRNA and protein expression of drug transporters and receptors at the BBB. These findings identify Tjap1 as a candidate regulator of both Golgi architecture and the BBB transporter profile in vitro, with potential implications for modulating drug transport across the BBB. - Source: PubMed
Publication date: 2026/05/28
Mi JunqiaoSchoder AnnabelleSun AiliMeybohm PatrickBurek Malgorzata - Metabolic reprogramming within the tumor microenvironment (TME) limits the efficacy of chemo-immunotherapy in triple-negative breast cancer (TNBC). Despite advances in high-resolution profiling, the specific intercellular metabolic crosstalk driving immune evasion remains incompletely understood. Here, we present a comprehensive single-cell metabolic atlas of the TNBC ecosystem to decode spatial and cell-type-specific metabolic vulnerabilities. Our multidimensional analysis reveals a distinct paracrine metabolic communication axis: CXCL9 macrophages upregulate rate-limiting enzymes (IDO1/2) to become a potential source of local kynurenine, which is subsequently imported by cytotoxic T cells. Through in vitro co-culture and in vivo models, we demonstrate that this kynurenine uptake triggers impaired effector function and phenotypic exhaustion. Crucially, pharmacological blockade of SLC7A5 with the specific inhibitor JPH203 abrogates this metabolic toxicity, restores T cell effector function, and enhances the anti-tumor efficacy of combined cisplatin and anti-PD-1 therapy. Collectively, our findings delineate the Kynurenine-SLC7A5 metabolic axis as a critical driver of immunosuppression, providing a compelling rationale for integrating amino acid transport blockade to overcome resistance to chemo-immunotherapy. - Source: PubMed
Publication date: 2026/06/25
Zhong SenYu BolinZhou ShengyiChen WenlongLiu FanglongZhu HuanhuanMin FangQian Fengyuan - Reprogramming of amino acid metabolism is crucial for the rapid proliferation of cancer cells, including cancer stem cells. However, the molecular mechanisms underlying this reprogramming in glioma stem cells (GSCs) remain poorly understood. Here, we report that the RNA-binding protein RBM12 increases the intracellular levels of large neutral amino acids, thereby activating the mTORC1 pathway and promoting GSC proliferation, self-renewal, and glioblastoma (GBM) growth. Mechanistically, RBM12 stabilizes the mRNA of the amino acid transporter SLC7A5, thereby increasing intracellular levels of large neutral amino acids, which subsequently activates the mTORC1 pathway. Further studies reveal that RBM12 enhances SLC7A5 mRNA stability by recruiting ALKBH5 to remove mA modifications on SLC7A5 mRNA. Importantly, pharmacological inhibition of the RBM12-SLC7A5 axis using the SLC7A5 inhibitor JPH203 effectively suppresses GBM growth. These findings elucidate a novel role for RBM12-SLC7A5 signaling in the malignant growth of GBM and highlight the therapeutic potential of targeting this axis for GBM treatment. - Source: PubMed
Publication date: 2026/06/22
Lei HongLuo WenlongZhou ShuWan LihaoLing PengHuang ZhihuaQian ZhihuaLu ChenfeiGuo MengyueXue ZhenQin JunZhao NingweiMan JianghongZhou WenchaoDong ZhiqiangXu ShutongZhou ZhipengWang XiuxingTao Weiwei - To investigate the potential molecular mechanisms underlying aspartame (APM)-induced malignant phenotypic changes in colorectal cancer (CRC). Candidate targets of APM were identified by integrating the ChEMBL, SwissTargetPrediction, and SEA databases. Differential expression analysis was performed using transcriptomic data from The Cancer Genome Atlas (TCGA) CRC cohort, followed by weighted gene co-expression network analysis (WGCNA) to identify key modules associated with CRC. The intersection of differentially expressed genes (DEGs), key module genes, and candidate APM targets was used to identify shared APM-CRC candidate genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, machine learning, SHAP-based interpretability analysis, molecular docking, and molecular dynamics simulations were then conducted to identify key feature genes and evaluate their potential interactions with APM. Finally, EdU, CCK-8, ROS fluorescence staining, and Western blot assays were performed in HCT116 and SW480 cells to validate the effects of APM on CRC cell proliferation, oxidative stress, and epithelial-mesenchymal transition (EMT)-related molecular alterations. A total of 4790 DEGs were identified between CRC and normal tissues, and WGCNA further identified key modules significantly associated with the tumor phenotype. Intersection analysis yielded 1003 CRC-related candidate genes and 26 shared APM-CRC candidate genes. Enrichment analysis indicated that these genes were mainly involved in extracellular matrix remodeling, regulation of cell adhesion, glutathione metabolism, and xenobiotic metabolism. Machine learning combined with SHAP analysis ultimately identified SLC7A5, MMP3, ITGA2, CAPN2, and BACE2 as key feature genes. Molecular docking and molecular dynamics simulations suggested that APM could potentially interact with all five key proteins, with MMP3 and ITGA2 showing relatively stronger binding affinity. In vitro experiments showed that APM increased the proliferation of HCT116 and SW480 cells, elevated intracellular ROS levels, and was associated with decreased E-cadherin expression and increased N-cadherin and Vimentin expression. These findings suggest that APM exposure may be associated with increased CRC cell proliferation and EMT-related molecular alterations, accompanied by changes in oxidative stress-related processes, extracellular matrix remodeling, and abnormal cell adhesion. SLC7A5, MMP3, ITGA2, CAPN2, and BACE2 may represent APM-responsive candidate molecules involved in these cellular responses. - Source: PubMed
Publication date: 2026/06/19
Liu QuanxiaYu DongQiao LijiaoWang NanFan WeiningWei TingtingTian ZhiqiangMa XiaoqiangXie Xiaoliang