Ask about this productRelated genes to: EFHD2 antibody
- Gene:
- EFHD2 NIH gene
- Name:
- EF-hand domain family member D2
- Previous symbol:
- -
- Synonyms:
- MGC4342
- Chromosome:
- 1p36.21
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-29
- Date modifiied:
- 2016-10-05
Related products to: EFHD2 antibody
Related articles to: EFHD2 antibody
- Radioresistance in colorectal cancer (CRC) remains a critical clinical challenge, with underlying mechanisms involving deoxyribonucleic acid (DNA) damage repair, metabolic reprogramming, and immune evasion. Here, we employed multi-omics approaches, including ribonucleic acid (RNA) sequencing, proteomic profiling, and lactyl-proteomics of radioresistant CRC cell models, combined with co-immunoprecipitation, molecular docking, spatial transcriptomics, and single-cell RNA sequencing. Functional validation included production of an EF-hand domain family member D2 (EFHD2) lysine 9 (K9) lactylation-specific antibody, T cell and macrophage co-culture assays, and multiplex immunofluorescence analyses, performed in vitro and in vivo using immunocompetent and immunodeficient mice, alongside patient-derived rectal cancer samples collected from our institution. We found that hsa-let-7b-5p was significantly downregulated in radioresistant CRC cells and tissues, correlating with poor prognosis. Restoration of hsa-let-7b-5p inhibited EFHD2, impaired homologous recombination through reduced activation of RAD51 recombinase (RAD51) and replication protein A2 (RPA2), prolonged phosphorylated histone H2AX at serine 139 (γH2AX) foci persistence, and increased oxidative stress and apoptosis after radiation. Mechanistically, EFHD2 interacted with high mobility group box 1 (HMGB1), enhancing lactate metabolism via hypoxia-inducible factor-1 alpha (HIF-1α) stabilization, with K9 lactylation of EFHD2 being essential for its DNA repair function. Elevated EFHD2-driven lactate reshaped the tumor immune microenvironment by promoting M2 macrophage polarization, suppressing antigen presentation, activating nuclear factor kappa-B (NF-κB) signaling, and upregulating programmed death-ligand 1 (PD-L1). Flow cytometry and immunohistochemistry revealed reduced CD4⁺/CD8⁺ T cell infiltration and increased forkhead box P3 positive (Foxp3⁺) regulatory T cells (Tregs) in EFHD2-high tumors, confirmed by spatial and single-cell transcriptomics showing immunosuppressive signatures. Importantly, combining EFHD2 knockdown with immune checkpoint blockade synergistically enhanced radiosensitivity and restored antitumor T cell responses. Collectively, these findings demonstrate that EFHD2 drives lactate-mediated immunosuppression and DNA repair to promote radioresistance in CRC, suggesting that targeting the EFHD2 axis may restore antitumor immunity and improve therapeutic outcomes. - Source: PubMed
Publication date: 2026/06/23
Yu YilinWu HaixiaXiao YuQiu JianjianHong LiangYang BaihuaWang JianminWang ZhipingShao LingdongXu BenhuaWu Junxin - This study aims to explore the cellular composition and transcriptional variability within the tumor microenvironment (TME) of non-small-cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNAseq) and to assess the role of EF-hand domain-containing protein 2 (EFHD2) in tumor progression and its involvement in relevant signaling pathways. - Source: PubMed
Publication date: 2026/03/21
Luo XuepingZhang FengLi ZhiyuZhong ChuchengShen Xiaozhen - Neurotropin, a non-protein extract widely used for the treatment of neuropathic pain, has recently been reported to protect against ischemic brain injury, enhance remyelination in demyelinating diseases, and ameliorate neuroinflammation and memory deficits. However, its role in microglial polarization and mitochondrial dysfunction in Alzheimer's disease (AD) remains poorly understood. In this study, we investigated the therapeutic potential of Neurotropin in the 5xFAD mouse model of AD. Neurotropin administration alleviated cognitive decline, reduced amyloid-β (Aβ) deposition, suppressed neuroinflammation, and preserved neuronal density. Mechanistically, Neurotropin improved mitochondrial morphology, restored ATP production, increased mitochondrial DNA copy number, and reduced oxidative stress while promoting a shift in microglial polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype. Transcriptomic and molecular analyses revealed that calcium homeostasis modulator family member 2 (Calhm2) was markedly upregulated in 5xFAD mice, colocalized with microglia, and transcriptionally regulated by fused in sarcoma (FUS), while Calhm2 interacted with EF-hand domain containing protein D2 (EFhd2). Neurotropin suppressed FUS-mediated Calhm2 transcription and attenuated Calhm2-EFhd2 interaction. Importantly, overexpression of Calhm2 in both microglial cells and 5xFAD mice abolished the beneficial effects of Neurotropin, leading to exacerbated mitochondrial dysfunction, oxidative stress, and inflammatory cytokine release. Together, these findings identify Calhm2 as a critical mediator of Neurotropin's neuroprotective effects and demonstrate that Neurotropin alleviates AD pathology by suppressing FUS-dependent Calhm2 transcription and blocking the Calhm2/EFhd2 interaction. This study provides new insights into the mechanism of Neurotropin action and highlights its therapeutic potential for AD. - Source: PubMed
Publication date: 2025/09/26
Huang YuanluWei FushengCheng XiaoeShi YinqiLiu ZiyeYe Lingling - Swiprosin-1 (SWS1/EFhd2) is a calcium-binding adaptor protein involved in cytoskeletal regulation, but its physiological role in bone homeostasis remains largely undefined. To elucidate its function in osteoclast biology, we examined SWS1 expression and activity during osteoclastogenesis using primary murine bone marrow-derived macrophages, siRNA-mediated knockdown, and SWS1 knockout (KO) mice. SWS1 was predominantly localized to the nucleus in precursor cells and redistributed to the F-actin ring in mature osteoclasts. Receptor activator of nuclear factor-kappa B ligand stimulation significantly downregulated SWS1 mRNA expression. Loss of SWS1 enhanced osteoclast formation, F-actin ring integrity, and bone resorption, accompanied by elevated expression of osteoclastogenic markers. In vivo, male SWS1 KO mice exhibited deteriorated trabecular bone microarchitecture with increased osteoclast numbers. Mechanistically, SWS1 deficiency intensified αvβ3 integrin-associated cytoskeletal signaling and upregulated Akt, MAPK, NF-κB, and PLCγ2 pathways. These results indicate that SWS1 negatively regulates osteoclast differentiation and function by restraining cytoskeletal reorganization and downstream signaling. Collectively, our findings establish SWS1 as a novel modulator of osteoclast activity and a potential therapeutic target for osteolytic bone disorders. - Source: PubMed
Publication date: 2025/09/04
Cheon Yoon-HeeKwak Sung ChulChung Chong HyukLee Chang HoonLee Myeung SuKim Ju-Young - This study investigates the expression pattern and functional significance of EF-hand domain-containing protein 2 (EFHD2) in hepatocellular carcinoma (HCC), with particular focus on its regulatory effects on tumor proliferation, migration, and invasion. Cellular experimental study was completed from June 2024 to January 2025 in the Basic Laboratory of the General Hospital of Southern Theater Command. TCGA database to determine EFHD2 expression and its clinicopathological correlations. GSCA database to assess methylation patterns and immune infiltration. Model of transient overexpression and knockdown of EFHD2 was constructed in hepatocellular carcinoma cells Hep3B, then RT-qPCR and Western blot were applied to verify the transfection efficiency. CCK-8 and colony formation assays for proliferation assessment, Transwell chambers for migration/invasion quantification. Protein-protein interaction networks were constructed via STRING, followed by GO/KEGG enrichment analysis. Statistical analysis was performed using the two independent samples -test. The results showed that EFHD2 demonstrated significant upregulation in HCC tissues versus normal controls (<0.05). Elevated EFHD2 expression correlated with advanced clinical stage (<0.05) and poor differentiation (<0.05). In the CCK-8 assay, the EFHD2 overexpression group demonstrated significantly higher cell viability than the control group, as evidenced by 450 nm relative absorbance values on Day 1 (0.529±0.019 0.515±0.016, =0.041, =0.320), Day 2 (1.356±0.019 1.094±0.042, =3.833, <0.001), Day 3 (2.817±0.049 2.143±0.124, =3.833, <0.001), and Day 4 (3.848±0.015 3.430±0.021, =0.469, <0.001). The EFHD2 knockdown group showed reduced cell viability compared to controls: Day 1 (0.541±0.020 0.552±0.015, =0.098, =0.423), Day 2 (1.154±0.009 1.326±0.029, =2.485, <0.001), Day 3 (2.453±0.041 2.653±0.031, =0.479, <0.001), and Day 4 (3.685±0.038 3.836±0.021, =6.804, <0.001). In colony formation assays, the overexpression group displayed a significant increase in colony numbers (254.667±23.861 186.000±16.703, =0.865, =0.015), whereas the knockdown group exhibited decreased colony formation (229.000±24.637 306.667±36.501, =0.988, =0.038). In Transwell assays, the EFHD2 overexpression group revealed enhanced migratory capacity [ (605.000±72.670) cells (472.667±28.095) cells, =2.462, =0.042] and invasive potential [(767.333±21.221) cells (414.333±16.623) cells, =0.331, <0.001]. The knockdown group showed attenuated migration [(311.000±71.084) cells (479.667±50.846) cells, =0.718, =0.029] and invasion [(247.667±48.263) cells (345.667±32.130) cells, =0.727, =0.043] compared to controls. The network of EFHD2-interacting proteins was further constructed by the STRING database, and the GO and KEGG analysis were used to perform bioinformatics analysis reveal that EFHD2 is mainly involved in actin cytoskeleton regulation. In conclusion, EFHD2 is highly expressed in HCC and is involved in the process of proliferation, migration and invasion of HCC. - Source: PubMed
Zhang Y MLi XJia X XLiu J ZLi W QXuan J FFeng S YSun Z HZhang W Y