Ask about this productRelated genes to: SLC22A3 antibody
- Gene:
- SLC22A3 NIH gene
- Name:
- solute carrier family 22 member 3
- Previous symbol:
- -
- Synonyms:
- OCT3, EMT
- Chromosome:
- 6q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-07-16
- Date modifiied:
- 2016-09-28
Related products to: SLC22A3 antibody
Related articles to: SLC22A3 antibody
- Vestibular schwannoma (VS) is a benign Schwann cell-derived tumor that frequently causes progressive hearing loss and vestibulocochlear dysfunction, substantially impacting quality of life. The molecular mechanisms underlying VS pathobiology remain poorly defined, and reliable biomarkers or targeted therapies are lacking. This study aimed to delineate the molecular landscape of VS through a transcriptome-wide meta-analysis. We performed a genome-wide random-effects meta-analysis of four independent Affymetrix microarray datasets from the Gene Expression Omnibus (GEO) database. Differential expression analyses were conducted with and without covariate adjustment. Gene Ontology enrichment and DrugBank-based drug-gene interaction analyses were subsequently applied to characterize biological pathways and assess translational potential. Across the meta-analysis, more than 3,200 differentially expressed genes were identified in the covariate-free model. After applying a more stringent threshold (|metaLFC| > 1 and FDR < 0.05), 1,095 genes remained differentially expressed, with high concordance between the covariate-free and covariate-adjusted models. Downregulated genes included extracellular matrix and stromal components (MFAP5, FABP4, DCN), and sensory- and synapse-related transcripts (SLC22A3, LGI1). Upregulated genes included immune- and inflammation-associated genes (TREM2, CCL3, CCL4, L1CAM) and proliferative regulators (CCND1, RAB31, MOXD1). Functional enrichment highlighted extracellular matrix remodeling, immune modulation, sensory signaling, and cell cycle pathways. Notably, many of the most strongly dysregulated genes have not previously been associated with VS. Drug-gene interaction analysis identified multiple dysregulated genes with known pharmacological targets, suggesting potential translational relevance. This transcriptome-wide meta-analysis provides a comprehensive overview of gene expression patterns in VS, highlighting alterations related to extracellular matrix organization, sensory and synaptic processes, immune-associated signaling, and cell cycle-related pathways. The study highlights novel disease-associated genes and pathways and may help prioritize candidates for further investigation, including those with potential relevance for therapeutic targeting. - Source: PubMed
Publication date: 2026/07/10
Altınalan EbrarPanina AleksandraFredriksson RobertŞakul Ayse ArzuSchiöth Helgi B - Triple-negative breast cancer (TNBC) remains a challenging and clinically aggressive subtype due to its heterogeneity and high mortality rate. Recent molecular subtyping has identified distinct TNBC subgroups with varying therapeutic responses, highlighting the need for targeted therapeutic strategies. The mesenchymal (MES) subtype is characterized by low immune cell infiltration, cancer stem cell-like features, and resistance to multiple drugs. Ferroptosis, a form of iron-dependent cell death, has emerged as a promising therapeutic strategy in TNBC due to the abundance of iron and lipids in tumor cells. However, ferroptosis sensitivity varies across different TNBC subtypes. Notably, the MES subtype exhibits resistance to ferroptosis despite elevated iron levels, due to impaired ferroptosis-executing mechanisms. This study investigates the role of SLC22A3, an organic cation transporter, which is enriched in MES tumors and positively correlates with markers of tumor stem cells. High SLC22A3 expression in MES-TNBC cells modulates serotonin uptake and metabolism, conferring ferroptosis resistance through two pathways. First, 5-HT(serotonin) acts as a radical-trapping antioxidant, eliminating lipid peroxides and inhibiting ferroptosis. Second, 5-HT induces histone serotonylation, which enhances histone methylation and facilitates the recognition of methylated histones by transcriptional initiation factors. This process activates SIRT1 transcription, inhibiting MAOA transcription mediated by FOXO1, thereby reducing 5-HT degradation and promoting ferroptosis resistance. Moreover, we identified potential SLC22A3 inhibitors and their synergistic combinations with ferroptosis inducers or cisplatin, which suppress tumor growth in both MES-subtype TNBC patient-derived organoids and in vivo, offering a promising strategy for personalized therapy. These findings suggest that targeting SLC22A3, along with ferroptosis inducers, may offer a promising therapeutic strategy for patients with MES-subtype TNBC.SLC22A3 affects serotonin uptake and metabolism in MES-TNBC cells, providing ferroptosis resistance through two mechanisms. 5-HT acts as a radical-trapping antioxidant, eliminating lipid peroxides and inhibiting ferroptosis. In addition, 5-HT induces histone serotonylation, which enhances histone methylation and facilitates the recognition of methylated histones by transcription initiation factors. This process activates SIRT1 transcription, inhibiting MAOA transcription mediated by FOXO1, thereby reducing 5-HT degradation and promoting ferroptosis resistance. TKIs served as SLC22A3 inhibitors and their combinations with RSL3 or cisplatin, which inhibit tumor growth in vivo, offering new personalized treatment options for MES-TNBC patients. - Source: PubMed
Publication date: 2026/07/09
Zhai DongshengLi WangChen GuoZhang WenliHu YueDeng LeleLi DengguoCheng HanZhou JixiangLi MingkaiWang LiZifan Lu - Metformin is a widely used drug with a relatively good efficacy in diabetes treatment, a good safety profile, and the potential for use in other indications. The variability in the individual responses to metformin therapy is partially determined by genetic factors. This narrative review aimed to summarize information on single nucleotide variant (SNVs) in genes for transporter proteins associated with metformin pharmacokinetics and pharmacodynamics and/or the occurrence of adverse effects. The Pharmacogenomics Knowledge Base (PharmGKB) and Web of Science databases were searched for metformin-associated gene variants that could affect its action. Seven transporter genes with twelve SNVs common in the European population were identified in the PharmGKB database, namely SNVs in genes (OCT1), (OCT2), (OCT3), (OCTN1), (MATE1), (MATE2-K) and (GLUT2); it is worth noting that GLUT2 is not metformin transported but a glucose transporter and as such, it can also influence metformin action. Based on 63 retrieved studies, the association of individual SNVs with metformin effectiveness and adverse effects is discussed. In view of the high variability of study designs, populations, and reporting patterns, we also propose a framework for the design and reporting of metformin-associated pharmacogenetic studies, suggesting also that determining a complete set of these SNVs could help in comprehensive understanding of genetically conditioned individual responsiveness to metformin therapy, thus opening the path to maximizing the utilization of its positive effects while minimizing the risk of adverse effects. In addition, given the large variability in designs among studies, we also propose a framework for future studies on SNVs in metformin action-associated transporters that could improve comparability of future studies. - Source: PubMed
Publication date: 2026/06/19
Mlcuchova NatalieLipovy BretislavZendulka OndrejJanosek JaroslavBorilova Linhartova Petra - Polycystic ovary syndrome is a prevalent, heterogeneous endocrine and metabolic disorder affecting approximately 10% of women of reproductive age, often characterized by hyperandrogenism, anovulation, and insulin resistance. Metformin, a first-line treatment for type 2 diabetes, is also widely prescribed for PCOS to reduce insulin resistance and induce ovulation. However, therapeutic response varies significantly across individuals, partly due to genetic variations in solute carrier (SLC) transporters. The organic cation transporter family, encoded by SLC22A1 (O15245), SLC22A2 (O15244), and SLC22A3 (O75751), facilitates metformin uptake into hepatocytes and renal excretion. Using an in silico pipeline, Align GVGD, PolyPhen-2, PROVEAN, PANTHER, PhD-SNP, and the ensemble predictor Meta-SNP, we screened 14 deleterious nonsynonymous SNPs. Solvent accessibility values were derived using NetSurfP, indicating that L42R (RSA: 0.54, ASA: 96.2 Å) and F422S (RSA: 0.49, ASA: 85.7 Å) are surface-exposed and likely to influence protein interaction. In contrast, R175L (RSA: 0.07, ASA: 18.4 Å) and T275M (RSA: 0.06, ASA: 21.1 Å) were buried and may impact local folding. ΔΔG predictions using MuPro ranged from -0.01745 to -1.99395, consistently indicating decreased protein stability. Structural models were built in SWISS-MODEL and validated via MolProbity scores (<1.5), ERRAT (>85%), and PROSA Z-scores (-6.8 to -8.2). Functional enrichment of the PPI network (STRING-DB) highlighted significant roles in drug transmembrane transport (GO:0006857, p = 2·3e-06), organic cation transport (GO:0015695, p = 4·7e-05), and xenobiotic metabolism pathways. These mutations may impair metformin pharmacokinetics and contribute to inter-individual therapeutic variability. While this study is limited by its computational design, the findings identify high-priority SNPs for future experimental validation, offering a foundation for precision pharmacogenomics in PCOS management. - Source: PubMed
Publication date: 2026/06/17
Harini RUsha BSatish RAkshatha PaiVijaya Kumar T M - Pancreatic cancer (PC) is a highly aggressive malignancy, with cancer stem cells (CSCs) playing a critical role in metastasis, therapy resistance, and recurrence, thereby presenting significant treatment challenges. Emerging evidence suggests that normal embryonic and adult progenitor stem cells share common gene signatures with CSCs. However, the early pluripotency-associated factors and stemness programs that become aberrantly reactivated during oncogenic transformation remain poorly defined. Here, we identify SLC22A3/OCT3 (Solute Carrier Family 22 Member 3) as a reactivated embryonic-associated signature that regulates PC stemness. SLC22A3 is markedly upregulated in CSC-enriched populations, and its silencing in PC cells grown in both 2D cultures and 3D organoid models significantly reduces key stemness features. Moreover, serotonin (5-HT) transport, mediated by SLC22A3, enhances overall stemness via downstream histone modifications, linking serotonin signaling to CSC regulation. Collectively, these findings establish SLC22A3 as a regulator of serotonin-driven stemness and a potential therapeutic target in PC. - Source: PubMed
Publication date: 2026/06/06
Krishna Kumar NivedetaVaradharaj VenkateshGayen NeelanjanaKaur Annant BirArikath KirtanaShah AshuMathivanan PoompozhilNallasamy PalanisamyAlsafwani Zahraa WajihSeshadri BhuvaneshwariRaut PratimaRauth SanchitaPersinger JimmieBrahma SandipanSchott MicahOberley-Deegan Rebecca ETalmon Geoffrey ACox Jesse LBatra Surinder KPonnusamy Moorthy P