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
- Breast ductal carcinoma in situ (DCIS) is often overtreated due to a lack of robust prognostic and predictive tools. This study aimed to evaluate gene expression in a well-characterised DCIS cohort to determine their clinical utility as biomarkers for ipsilateral recurrence. RNA was extracted from microdissected tissues from primary DCIS. A 129-gene panel was analysed using NanoString in 174 DCIS cases (131 with no recurrence and 43 with recurrence). Association with recurrence was determined by Cox regression analyses. Validation was performed by immunohistochemistry. A new 7-gene panel (PBK, COL1A2, GSTM5, MMP2, MX1, SLC22A3 and ZEB1) was derived from the NanoString data but could not be validated in external datasets, including when stratified by radiotherapy treatment. Increased expression of ZEB1 alone was consistently significantly associated with longer recurrence-free survival in discovery and validation cohorts (hazard ratios 0.56-0.71). Correlation between mRNA and protein expression showed the strongest association with peri-ductal fibroblast expression. However, there was no association of ZEB1 protein expression in these cells with recurrence in an independent cohort. Existing multigene panels showed inconsistent associations with recurrence in the current cohort. Gene expression panels show limited reproducibility across cohorts, highlighting the need for prospective trials and context-specific validation. ZEB1 mRNA emerges as a potential biomarker warranting further investigation for its clinical utility in guiding management decisions in DCIS. - Source: PubMed
Publication date: 2026/09/24
Un AlexandriaMahale SakshiByrne DavidLesche DorotheaMartinez-Perez CarlosPang Jia-MinPechlivanis MareeSaunders HugoJayawardana Madawa WLuo TongtongJayasinghe Sureshni IKader TanjinaDevereux LisaTan Puay HoonGreen Andrew RRakha Emad ATurnbull Arran KFox Stephen BMann G BruceGorringe Kylie L - The widespread use of Wi-Fi-derived radiofrequency electromagnetic radiation (RF-EMR) has raised concerns regarding male reproductive health; however, whether paternal exposure exerts transgenerational effects on offspring development remains unclear. This study investigated the effects of chronic paternal 2.4 GHz Wi-Fi RF-EMR exposure (whole-body SAR 0.125-0.5 W/kg, 4 h/day, 6 days/week for 20 weeks) on sperm quality in F0 male mice and placental development in F1 offspring, with a focus on epigenetic regulation. Paternal RF-EMR exposure significantly reduced sperm concentration and increased the sperm abnormality rate in F0 males. F1 offspring exhibited reduced fetal weight and placental efficiency, with more pronounced impairments in male offspring. Mechanistically, paternal exposure reduced the proportion of placental labyrinth layer and downregulated multiple nutrient transporters in a male-biased manner. Epigenetic analysis revealed sex-dependent histone modifications in placentas following paternal RF-EMR exposure: male placentas exhibited increased H3K9me2/3, H3K27me3, H3K27ac, and H3K4me2, whereas female placentas exhibited decreased H3K4me2. ChIP-qPCR targeting transporter promoters revealed sex-specific enrichment of repressive histone marks in placentas from exposed fathers. In male placentas, H3K27me3 was increased at the Atp1a1 and Slc22a3 promoters, and H3K9me3 was increased at the Atp1a1 and Slc2a1 promoters. In female placentas, H3K27me3 at the Slc3a2 promoter was significantly decreased. Collectively, chronic paternal Wi-Fi RF-EMR exposure impairs fetal growth and placental efficiency, with male offspring being more susceptible, and is associated with disrupted placental structure, impaired nutrient transport, and sex-dependent histone modifications in the offspring placenta. These findings underscore the importance of considering paternal RF-EMR exposure in reproductive risk assessment. - Source: PubMed
Publication date: 2026/09/03
Wang JunGao LingxiaJin NiYan SongLei HuiJu YingChen ShuqiangWang Xiaohong - 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