DHX34 antibody - middle region (ARP36417_P050)
- Known as:
- DHX34 (anti-) - middle region (ARP36417_P050)
- Catalog number:
- arp36417_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- DHX34 antibody - middle region (ARP36417_P050)
Related genes to: DHX34 antibody - middle region (ARP36417_P050)
- Gene:
- DHX34 NIH gene
- Name:
- DExH-box helicase 34
- Previous symbol:
- DDX34
- Synonyms:
- KIAA0134
- Chromosome:
- 19q13.32
- Locus Type:
- gene with protein product
- Date approved:
- 2001-11-27
- Date modifiied:
- 2016-10-05
Related products to: DHX34 antibody - middle region (ARP36417_P050)
Related articles to: DHX34 antibody - middle region (ARP36417_P050)
- t(8;21) acute myeloid leukemia (AML) is driven by AML1-ETO, which undergoes alternative splicing to generate AML1-ETO9a (AE9a), a truncated isoform with enhanced leukemogenic activity. Although t(8;21) AML is considered favorable-risk, clinical outcomes are heterogeneous, and AE9a expression varies markedly among patients. How cells restrain this oncogenic isoform remains unclear. Here, we identify nonsense-mediated mRNA decay (NMD) as an isoform-specific buffer of AE9a dosage. Inclusion of the ETO9a cassette exon introduces premature termination codons and generates an NMD-sensitive transcript. In primary t(8;21) AML CD34⁺ hematopoietic stem and progenitor cells, AE9a inclusion inversely correlated with NMD-factor expression, and high EIF4A3 expression was associated with improved overall survival specifically in t(8;21) AML, but not in other AML subtypes. Pharmacological inhibition of SMG1 or EIF4A3 and genetic depletion of NMD factors increased AE9a abundance in t(8;21) AML cell lines and primary patient cells, with cytoplasmic transcript accumulation and increased AE9a protein. Conversely, EIF4A3 overexpression reduced AE9a RNA and protein, restrained t(8;21) AML cell growth, spared healthy CD34⁺ progenitor expansion, and enhanced idarubicin sensitivity. These findings define EIF4A3-dependent NMD as a checkpoint linking RNA surveillance to oncogenic fusion-isoform dosage, leukemic fitness, and chemosensitivity in t(8;21) AML, providing a mechanistic explanation for clinical heterogeneity in t(8;21) AML. EIF4A3-dependent NMD buffers AE9a dosage and modulates t(8;21) AML cell fitness and chemosensitivity: Schematic model summarizing the proposed AE9a-NMD axis in t(8;21) AML. Alternative splicing of AML1-ETO generates the ETO9a cassette exon, producing a PTC-containing AE9a transcript. After nuclear export, ribosome engagement with the PTC-containing AE9a mRNA recruits the NMD machinery, including UPF factors, SMG factors, DHX34, and the exon-junction complex component EIF4A3. Efficient NMD promotes AE9a mRNA decay and limits AE9a protein accumulation. High EIF4A3/NMD activity therefore lowers AE9a dosage, restrains t(8;21) AML cell proliferation, enhances chemosensitivity to idarubicin, and is associated with improved patient survival. Conversely, impaired NMD activity permits AE9a accumulation and may increase leukemic fitness. This model defines an isoform-specific, NMD-buffered oncogenic dosage checkpoint in t(8;21) AML. - Source: PubMed
Publication date: 2026/07/14
Zhang MinLi YishengZhang BinCai ChenLi ShuyiHe ZhijieMeng XiangyuWang ChengguangDing WeichaoWang XiaoqiDong XingliLi YonghuiYu Li - Tumor-associated macrophages (TAMs) are the dominant myeloid population in hepatocellular carcinoma (HCC) and critically shape the chemokine milieu that governs CD8 T-cell entry. However, how macrophage-intrinsic regulators of chemokine expression influence antitumor immunity and response to immunotherapy remains unclear. We postulated that the macrophage RNA helicase DEAH-box helicase 34 (DHX34) suppresses production of the chemokine fractalkine (CX3CL1), thereby limiting chemotaxis of CX3CR1 CD8 T cells and diminishing the therapeutic efficacy of programmed cell death protein-1 (PD-1) blockade. We therefore examined the impact of macrophage DHX34 on T-cell trafficking and tumor control. - Source: PubMed
Publication date: 2025/12/13
Li ZeyuYuan JianingDu FeiLiu NanbinZhang ChunliHuang LiminFeng JunZhang ChenLiu XiSun JinHe GaixiaLiu GuoyingLi ZongfangTian Hongwei - Although cadmium (Cd) exposure has been implicated in lung cancer development, systematic investigations into its association with cancer mortality, particularly lung cancer mortality remain limited, and the molecular mechanisms driving Cd-induced tumor progression are not fully understood. In this study, we first conducted a meta-analysis of existing cohort studies to quantitatively assess the association between Cd exposure and cancer- and lung cancer-specific mortality. We then employed an integrative approach combining bioinformatics analyses, LASSO regression, and Mendelian randomization to identify and validate DHX34 as a key gene implicated in Cd-related lung carcinogenesis. These findings were further supported by molecular docking, molecular dynamics simulations, in vitro functional assays, and in vivo tumor models. Our meta-analysis showed that long-term Cd exposure significantly increased cancer mortality risk, especially in males (RR = 1.49, 95 % CI: 1.13-1.96) and in lung cancer (RR = 1.86, 95 % CI: 1.36-2.54). Integration of GSE165549 and TCGA data identified 36 Cd-related genes enriched in tumor associated pathways including cell cycle and DNA replication. LASSO regression and Mendelian randomization suggested a causal role of DHX34 in lung cancer. Molecular docking demonstrated a strong binding affinity between Cd and DHX34 (binding free energy = -5.34 kcal/mol), and molecular dynamics simulations confirmed the stability of this complex. Functional assays further showed that CdCl exposure upregulated DHX34, thereby promoting lung cancer cell proliferation and tumor growth both in vitro and in vivo. Together, these findings provide multi-level evidence that DHX34 mediates Cd-induced lung cancer progression, highlighting the carcinogenic potential of environmental heavy metal exposure and offering new insights into molecular targets for early prevention, risk stratification, and therapeutic intervention. - Source: PubMed
Publication date: 2025/09/19
Lu YongbinKong WeizeWang KaiwenShao ZicongHui XuSong XupingZhang SiyuMa LiCheng ZhiyuanSu FeiZhang TaoYang Kehu - Tumors often evade immune surveillance by crippling their immunogenicity in the microenvironment. DHX34, an RNA helicase involved in nonsense-mediated mRNA decay pathway, is critical for aberrant RNA degradation. However, the effect of DHX34 in regulating the immunogenicity in hepatocellular carcinoma (HCC) is still unclear. Here, a surprising function of DHX34 in inhibited HCC immunogenicity is identified. DHX34-deficient tumors were infiltrated by activated T cells that impaired tumor growth and enhanced survival in mice. Mechanistically, DHX34 depletion triggered dsRNA accumulation which may activate cytosolic RNA-sensing pathway effectors such as MAVS, p-IKK, p-IRF3, and the subsequent type-I interferon response, evoking tumor-intrinsic immunity and leading to CD8 T activation. Collectively, DHX34 is implicated as a regulator that orchestrates a barrier in HCC by suppressing dsRNA-driven innate immune activation. Targeting DHX34 may enhance tumor immunogenicity and synergize with immunotherapies, offering a novel therapeutic strategy for HCC. - Source: PubMed
Publication date: 2025/06/30
Zhang ChunliHuang LiminLi ZeyuWang QianLiu NanbinZhang ChongyuLiu XiZhang ChenHe GaixiaSun JinLi ZongfangTian Hongwei - As a member of the DExD/H-box RNA helicase family, DHX34 has demonstrated a significant correlation with the development of multiple disorders. Nevertheless, a comprehensive investigation between DHX34 and pan-cancer remains unexplored. We analyzed the value of DHX34 in pan-cancer based on some databases, such as The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and The Human Protein Atlas (HPA) by use the R language as well as some online analysis tools, including STRING, TISIDB, TISCH2. And based on our samples we performed Western blot (WB), qPCR and immunohistochemical staining (IHC) experiments. DHX34 was highly expressed in most tumors, including Liver Hepatocellular Carcinoma (LIHC), compared to corresponding normal tissues. Among cervical cancers, DHX34 mutation frequency was the highest. Intriguingly, a positive correlation was observed between DHX34 expression and Mutational Burden (TMB) across 12 tumor types, and Microsatellite Instability (MSI) across 10 tumor types. Remarkably, DHX34 exhibited a favorable diagnostic value in a multitude of tumors. High expression of DHX34 is associated with poor prognosis in tumors such as adrenocortical carcinoma (ACC), renal papillary cell carcinoma (KIRP), low-grade glioma (LGG), and LIHC. Correlation analysis indicated that DHX34 expression correlated with clinicopathological features in a variety of tumors. The Protein-Protein Interaction (PPI) network and GSCALite database suggested that DHX34 and its ten co-expression genes might promote cancer progression by regulating the cell cycle. Gene Set Enrichment Analysis (GSEA) results further showed that DHX34 was positively correlated with pathways such as cell cycle, mitosis, and gene transcription regulation. The TISIDB database showed that DHX34 expression was closely associated with immune infiltration. Based on the TISCH2 database, we found that DHX34 was expressed in a number of immune cells, with relatively high expression in monocyte macrophages in LIHC. In summary, our study found that DHX34 is highly expressed in pan-cancer and has diagnostic and prognostic value. Targeting DHX34 may improve the therapeutic efficacy of immunotherapy and chemotherapy in a multitude of tumors. - Source: PubMed
Publication date: 2024/10/28
Liu NanbinWang QianZhu PengpengHe GaixiaLi ZeyuChen TingYuan JianingLa TingTian HongweiLi Zongfang