ArticleThe Journal of biological chemistry2014
DNA promoter methylation-dependent transcription of the double C2-like domain β (DOC2B) gene regulates tumor growth in human cervical cancer.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction.Cell communication and signaling : CCS · 2025Article
- The HRAS-binding C2 domain of PLCη2 suppresses tumor-like synoviocytes and experimental arthritis in rheumatoid arthritis.Experimental & molecular medicine · 2025Article
- Biological functions of extracellular vesicle double C2-like domain beta in cervical cancer.Scientific reports · 2025Article
- Regulation and tumor-suppressive function of the miR-379/miR-656 (C14MC) cluster in cervical cancer.Molecular oncology · 2024Article
- Metastatic suppression by DOC2B is mediated by inhibition of epithelial-mesenchymal transition and induction of senescence.Cell biology and toxicology · 2022Article
- Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.Frontiers in endocrinology · 2022Review
- ZNF471 modulates EMT and functions as methylation regulated tumor suppressor with diagnostic and prognostic significance in cervical cancer.Cell biology and toxicology · 2021Article
- Analysis of Nuclear Encoded Mitochondrial Gene Networks in Cervical Cancer.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection.International journal of molecular sciences · 2021Review
- TC2N: A Novel Vital Oncogene or Tumor Suppressor Gene In Cancers.Frontiers in immunology · 2021Review
- Pan-Cancer Multiomics Analysis of TC2N Gene Suggests its Important Role(s) in Tumourigenesis of Many Cancers.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Tac2-N serves an oncogenic role and promotes drug resistance in human gastric cancer cells.Experimental and therapeutic medicine · 2020Article
- TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer.Cell death and differentiation · 2019Article
- Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2018Article
- The Progress of Methylation Regulation in Gene Expression of Cervical Cancer.International journal of genomics · 2018Review
- Recent findings on epigenetic gene abnormalities involved in uterine cancer.Molecular and clinical oncology · 2017Article
- Exocytosis proteins as novel targets for diabetes prevention and/or remediation?American journal of physiology. Regulatory, integrative and comparative physiology · 2017Review
- Gene promoter-associated CpG island hypermethylation in squamous cell carcinoma of the tongue.Virchows Archiv : an international journal of pathology · 2017Article
- Genetics of multifactorial disorders: proceedings of the 6th Pan Arab Human Genetics Conference.Journal of translational medicine · 2016Article
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10 authors.
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Abstract
Double C2-like domain β (DOC2B) gene encodes for a calcium-binding protein, which is involved in neurotransmitter release, sorting, and exocytosis. We have identified the promoter region of the DOC2B gene as hypermethylated in pre-malignant, malignant cervical tissues, and cervical cancer cell lines by methylation-sensitive dimethyl sulfoxide-polymerase chain reaction and bisulfite genome sequencing; whereas, it was unmethylated in normal cervical tissues (p < 0.05). The promoter hypermethylation was inversely associated with mRNA expression in SiHa, CaSki, and HeLa cells and treatment with demethylating agent 5-aza-2-deoxycytidine restored DOC2B expression. The region -630 to +25 bp of the DOC2B gene showed robust promoter activity by a luciferase reporter assay and was inhibited by in vitro artificial methylation with Sss1 methylase prior to transient transfections. Overexpression of the DOC2B gene in SiHa cells when compared with controls showed significantly reduced colony formation, cell proliferation, induced cell cycle arrest, and repressed cell migration and invasion (p < 0.05). Ectopic expression of DOC2B resulted in anoikis-mediated cell death and repressed tumor growth in a nude mice xenograft model (p < 0.05). DOC2B expressing cells showed a significant increase in intracellular calcium level (p < 0.05), impaired AKT1 and ERK1/2 signaling, and induced actin cytoskeleton remodeling. Our results show that promoter hypermethylation and silencing of the DOC2B gene is an early and frequent event during cervical carcinogenesis and whose reduced expression due to DNA promoter methylation may lead to selective cervical tumor growth.
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