ArticleMolecular medicine (Cambridge, Mass.)2012
Homeobox D10 gene, a candidate tumor suppressor, is downregulated through promoter hypermethylation and associated with gastric carcinogenesis.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis.BMC cancer · 2020Pooled it
- HOX and MEINOX in cellular plasticity, fibrosis, and cancer.World journal of stem cells · 2025Review
- The HOX Gene Family's Role as Prognostic and Diagnostic Biomarkers in Hematological and Solid Tumors.Cancers · 2025Review
- Effects of HOX family regulator-mediated modification patterns and immunity characteristics on tumor-associated cell type in endometrial cancer.Molecular biomedicine · 2024Article
- Gastrodin Induces Ferroptosis of Glioma Cells via Upregulation of Homeobox D10.Molecules (Basel, Switzerland) · 2023Article
- Upregulation of homeobox D10 expression suppresses invasion and migration of clear cell renal cell carcinoma through targeting of E-cadherin.Molecular biology reports · 2022Article
- Identification and Validation of Esophageal Squamous Cell Carcinoma Targets for Fluorescence Molecular Endoscopy.International journal of molecular sciences · 2021Article
- Prognostic and clinical significance of HOXC9 and HOXD10 in papillary thyroid cancer.Translational cancer research · 2021Article
- RestoringFrontiers in oncology · 2021Article
- Identification of HOXD10 as a Marker of Poor Prognosis in Glioblastoma Multiforme.OncoTargets and therapy · 2021Article
- Methylation inCells · 2020Review
- Frequent promoter methylation of HOXD10 in endometrial carcinoma and its pathological significance.Oncology letters · 2020Article
- The effect of overexpression of theGland surgery · 2020Article
- BioTarget: A Computational Framework Identifying Cancer Type Specific Transcriptional Targets of Immune Response Pathways.Scientific reports · 2019Article
- Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway.Cell communication and signaling : CCS · 2019Article
- Identification of IDH-mutant gliomas by a prognostic signature according to gene expression profiling.Aging · 2018Article
- Validation of epigenetic mechanisms regulating gene expression in canine B-cell lymphoma: An in vitro and in vivo approach.PloS one · 2018Article
- Transcriptome analysis in primary colorectal cancer tissues from patients with and without liver metastases using next-generation sequencing.Cancer medicine · 2017Article
- Silencing HOXD10 by promoter region hypermethylation activates ERK signaling in hepatocellular carcinoma.Clinical epigenetics · 2017Article
- Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions.Journal of Cancer · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeobox D10 (HoxD10 ) gene plays a critical role in cell differentiation and morphogenesis during development. However, the function of HoxD10 in tumor progression remains largely unknown. We demonstrate that the expression of HoxD10 is commonly downregulated in gastric cancer tissues (n = 33) and cell lines (n = 8) relative to normal stomach tissues. Functionally, reexpression of HoxD10 results in significant inhibition of cell survival, induction of cell apoptosis, and impairment of cell migration and invasion. Moreover, ectopic expression of HoxD10 suppresses gastric tumor growth in a mouse xenograft model. To identify target candidates of HoxD10, we performed cDNA microarray and showed that HoxD10 regulates multiple downstream genes including IGFBP3. Reintroduction of HoxD10 transcriptionally upregulates IGFBP3, activates caspase 3 and caspase 8, and subsequently induces cell apoptosis. Methylation specific PCR revealed that HoxD10 promoter DNA was hypermethylated in gastric cancer cell lines. Additionally, 5-aza demethylation treatment could transiently reactivate the expression of HoxD10 in gastric cancer cells. HoxD10 promoter methylation frequently was detected in gastric cancer tissues obtained from endoscopic biopsies (85.7%, 24/28) and surgically resected samples (82.6%, 57/69). Intestinal metaplasia tissues showed a 60% methylation rate (18/30), but no detectable methylation in normal stomach tissues (0%, 0/10). Taken together, our results suggest that HoxD10 functions as a candidate tumor suppressor in gastric cancer, which is inactivated through promoter hypermethylation.
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