ArticleCell & bioscience2016
Knockdown of CLIC4 enhances ATP-induced HN4 cell apoptosis through mitochondrial and endoplasmic reticulum pathways.
Article in Cell & bioscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 40 citations in OpenAlex.
- The role of chloride intracellular channel 4 in tumors.Cancer cell international · 2025Review
- The pursuit of novel head and neck cancer biomarkers - tissue and blood expression of chloride intracellular channels family.PloS one · 2025Article
- Identification of mitochondrial ATP synthase as the cellular target of Ru-polypyridyl-National science review · 2024Article
- Retrograde AAV-mediated gene modulation reveals chloride intracellular channel proteins as potent regulators of retinal ganglion cell death.Experimental neurology · 2024Article
- Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy.World journal of clinical oncology · 2023Review
- Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers.Cells · 2023Review
- Identification of Potential Biomarkers Using Integrative Approach: A Case Study of ESCC.SN computer science · 2023Article
- Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein.Computational and structural biotechnology journal · 2023Article
- Article
- ATP-induced cell death: a novel hypothesis for osteoporosis.Frontiers in cell and developmental biology · 2023Review
- Article
- CLIC4 localizes to mitochondrial-associated membranes and mediates cardioprotection.Science advances · 2022Article
- Mitochondrial ion channels in pancreatic β-cells: Novel pharmacological targets for the treatment of Type 2 diabetes.British journal of pharmacology · 2021Review
- Long non-coding RNA TDRG1 facilitates cell proliferation, migration and invasion in breast cancer via targeting miR-214-5p/CLIC4 axis.Cancer biology & therapy · 2021Article
- Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Review
- Intracellular Chloride Channels: Novel Biomarkers in Diseases.Frontiers in physiology · 2020Review
- Article
- Resveratrol reduces store-operated CaBiological research · 2019Article
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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
backgroundHuman head and neck squamous carcinoma is the 6th most prevalent carcinoma worldwide. Although many novel therapies have been developed, the clinical treatment for patients remains non-ideal. Chloride intracellular channel 4 (CLIC4), one of the seven members of the CLIC family, is a newly found Cl(-) channel that participates in various biological processes, including cellular apoptosis and differentiation. Accumulating evidence has revealed the significant role of CLIC4 in regulating the apoptosis of different cancer cells. Here, we investigated the functional role of CLIC4 in the apoptosis of HN4 cells, a human head and neck squamous carcinoma cell line.
resultsIn the present study, we used immunohistochemical staining to demonstrate that the expression level of CLIC4 is elevated in the tissue of human oral squamous carcinoma compared with healthy human gingival tissue. Specific CLIC4 small interfering RNA was used to knockdown the expression of CLIC4. The results showed that knockdown of CLIC4 with or without 100 μM adenosine triphosphate (ATP) treatment significantly increased the expression of Bax, active caspase 3, active caspase 4 and CHOP but suppressed Bcl-2 expression in HN4 cells. Moreover, the results from the TdT-mediated dUTP nick end labeling assay indicated that CLIC4 knockdown induced a higher apoptotic rate in HN4 cells under the induction of ATP. In addition, knockdown of CLIC4 dramatically enhanced ATP-induced mitochondrial membrane depolarization in HN4 cells. Moreover, intracellular Ca(2+) measurement revealed that Ca(2+) release induced by ATP and thapsigargin, a Ca(2+)-ATPase inhibitor of the endoplasmic reticulum, was significantly enhanced by the suppression of CLIC4 in HN4 cells.
conclusionsKnockdown of CLIC4 enhanced ATP-induced apoptosis in HN4 cells. Both the pathways of mitochondria and endoplasmic reticulum stress were involved in CLIC4-mediated cell apoptosis. Based on our finding, CLIC4 may be a potential and valuable target for the clinical treatment of head and neck squamous carcinoma.
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