ArticleJournal of Cancer2017
Sine Oculis Homeobox Homolog 1 Regulates Mitochondrial Apoptosis Pathway Via Caspase-7 In Gastric Cancer Cells.
Article in Journal of Cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The Significance of SIX1 as a Prognostic Biomarker for Survival Outcome in Various Cancer Patients: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Deciphering the role ofWorld journal of hepatology · 2025Review
- Induction of Apoptosis by Ethanol, Methanol, and Ethyl Acetate Extracts fromInternational journal of fertility & sterility · 2025Article
- Sine oculis homeobox homolog family function in gastrointestinal cancer: Progression and comprehensive analysis.World journal of clinical oncology · 2025Review
- Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics.Heliyon · 2024Review
- SIX1 Downregulation Suppresses Self-renewal Capacity and THY1 Expression in Hepatocellular Carcinoma and SIX1 Dominate the Survival in Liver Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study.Frontiers in cell and developmental biology · 2022Article
- Novel Potential Therapeutic Target for E2F1 and Prognostic Factors of E2F1/2/3/5/7/8 in Human Gastric Cancer.Molecular therapy. Methods & clinical development · 2020Article
- miR-489-3p/SIX1 Axis Regulates Melanoma Proliferation and Glycolytic Potential.Molecular therapy oncolytics · 2020Article
- MiR-203a-3p regulates TGF-β1-induced epithelial-mesenchymal transition (EMT) in asthma by regulating Smad3 pathway through SIX1.Bioscience reports · 2020Article
- The treatment role ofBioscience reports · 2019Article
- The Sineoculis Homeobox Homolog 1 (SIX1) Gene Regulates Paclitaxel Resistance by Affecting Reactive Oxygen Species and Autophagy in Human Hepatocellular Carcinoma Cell Line HepG2.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- microRNA-488 inhibits chemoresistance of ovarian cancer cells by targeting Six1 and mitochondrial function.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sine oculis homeobox homolog 1 (Six1) is crucial in normal organ development. Recently, Six1 is reported to display aberrant expression in various cancers and plays important roles in cancer development. However, the regulatory mechanism of Six1 in gastric cancer is largely unknown. In the current study, we found that Six1 was increased in gastric cancer tissues, and its upregulation significantly associated with lymph node metastasis (p=0.042) and poor differentiation (p=0.039). Next, we took advantage of public available microarray data to assess Six1 prognostic value with online K-M Plotter software in gastric cancer, which demonstrated that patients with higher Six1 expression had shorter survival time (p=0.02). To explore the underlying mechanism of Six1, we silenced its upregulation in gastric cells to detect cellular functions. Our results indicated that knock-down Six1 could decrease colony formation number and rendered cells sensitive to 5- Fluorouracil drug treatment. The flow cytometry analyses showed that Six1 silence could promote apoptosis but had little effect on cell cycle transition. Along this clue, we tested mitochondrial membrane potential with JC-1 assay, which suggested that Six1 inhibition could trigger mitochondrial apoptosis. Our subsequent results revealed that Six1 knock-down could reduce the level of anti-apoptotic protein Bcl-2, and caspase-7 but not caspase-3 was involved to execute the mitochondrial apoptosis pathway. Taken together, we find Six1 has oncogenic role in gastric cancer development, and silenced Six1 expression can promote mitochondrial apoptosis by repressing Bcl-2 and activating executor caspase-7. These findings suggest that Six1 may become a valuable prognostic and therapeutic target in gastric cancer.
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Registered trials
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