ClC-3 Chloride Channel Proteins Regulate the Cell Cycle by Up-regulating cyclin D1-CDK4/6 through Suppressing p21/p27 Expression in Nasopharyngeal Carcinoma Cells

It was shown in this study that knockdown of ClC-3 expression by ClC-3 siRNA prevented the activation of hypotonicity-induced chloride currents and arrested cells at the G0/G1 phase in nasopharyngeal carcinoma CNE-2Z cells. Reconstitution of ClC-3 expression with ClC-3 expression plasmids could rescue the cells from the cell cycle arrest caused by ClC-3 siRNA treatments. Transfection of cells with ClC-3 siRNA decreased the expression of cyclin D1, cyclin dependent kinase 4 and 6 and increased the expression of cyclin dependent kinase inhibitors (CDKIs), p21 and p27. Pretreatments of cells with p21 and p27 siRNAs depleted the inhibitory effects of ClC-3 siRNA on the expression of CDK4 and CDK6, but not on that of cyclin D1, indicating the requirement of p21 and p27 for the inhibitory effects of ClC-3 siRNA on CDK4 and CDK6 expression. ClC-3 siRNA inhibited cells to progress from the G1 phase to the S phase, but pretreatments of cells with p21 and p27 siRNAs abolished the inhibitory effects of ClC-3 siRNA on the cell cycle progress. Our data suggest that ClC-3 may regulate cell cycle transition between G0/G1 and S phases by up-regulation of the expression of CDK4 and CDK6 through suppression of p21 and p27 expression.

• Publication year

  2016

• Venue

  Scientific Reports

• Publication date

  2016-07-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/srep30276PMID 27451945PMCID 4959003
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Transcription Repressor REST in Adult Neurons: Physiology, Pathology, and Diseases,,

  2015cited by this paper
• ClC-3 is an intracellular chloride/proton exchanger with large voltage-dependent nonlinear capacitance.

  2013cited by this paper
• Tamoxifen inhibits migration of estrogen receptor‐negative hepatocellular carcinoma cells by blocking the swelling‐activated chloride current

  2013cited by this paper
• The ClC-3 chloride channel protein is a downstream target of cyclin D1 in nasopharyngeal carcinoma cells.

  2013cited by this paper
• Cell biology and physiology of CLC chloride channels and transporters.

  2012cited by this paper
• Differential expression and roles of volume-activated chloride channels in control of growth of normal and cancerous nasopharyngeal epithelial cells.

  2012cited by this paper
• Cell cycle-dependent subcellular distribution of ClC-3 in HeLa cells

  2012cited by this paper
• ClC-3 is a candidate of the channel proteins mediating acid-activated chloride currents in nasopharyngeal carcinoma cells.

  2012cited by this paper
• ClC‐3 is a main component of background chloride channels activated under isotonic conditions by autocrine ATP in nasopharyngeal carcinoma cells

  2011cited by this paper
• A Critical Role for Chloride Channel-3 (CIC-3) in Smooth Muscle Cell Activation and Neointima Formation

  2011cited by this paper
• The ClC-3 chloride channels in cardiovascular disease

  2011cited by this paper
• Cardiac-specific, inducible ClC-3 gene deletion eliminates native volume-sensitive chloride channels and produces myocardial hypertrophy in adult mice.

  2010cited by this paper
• NADPH Oxidases: Functions and Pathologies in the Vasculature

  2010cited by this paper
• Activation of Swelling-activated Chloride Current by Tumor Necrosis Factor-α Requires ClC-3-dependent Endosomal Reactive Oxygen Production*

  2010cited by this paper
• Functional and molecular characterizations of chloride channels in rat pleural mesothelial cells.

  2009cited by this paper
• Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis.

  2009cited by this paper
• Expressions of p53, cyclinD1 and histopathological features in basal cell carcinomas.

  2009cited by this paper
• Electrophysiology of Reactive Oxygen Production in Signaling Endosomes

  2009cited by this paper
• p21/Cip1 and p27/Kip1 Are essential molecular targets of inositol hexaphosphate for its antitumor efficacy against prostate cancer.

  2009cited by this paper
• Pathophysiology and puzzles of the volume‐sensitive outwardly rectifying anion channel

  2009cited by this paper
• Regulation of cell proliferation by intermediate-conductance Ca2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells.

  2008cited by this paper
• Suppression of ClC-3 channel expression reduces migration of nasopharyngeal carcinoma cells.

  2008cited by this paper
• Silence of ClC‐3 chloride channel inhibits cell proliferation and the cell cycle via G1/S phase arrest in rat basilar arterial smooth muscle cells

  2008cited by this paper
• ClC3 Is a Critical Regulator of the Cell Cycle in Normal and Malignant Glial Cells

  2008cited by this paper
• Survivin and cyclin D1 are jointly expressed in thyroid papillary carcinoma and microcarcinoma.

  2008cited by this paper
• Cyclin D1 and p27 expression as prognostic factor in papillary carcinoma of thyroid: association with clinicopathological parameters.

  2008cited by this paper
• Amplification of c‐myc and cyclin D1 genes in primary and metastatic carcinomas of the liver

  2007cited by this paper
• Cytokine Activation of Nuclear Factor &kgr;B in Vascular Smooth Muscle Cells Requires Signaling Endosomes Containing Nox1 and ClC-3

  2007cited by this paper
• Cyclin D1 and p16 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid gland

  2007cited by this paper
• Roles of volume‐activated Cl− currents and regulatory volume decrease in the cell cycle and proliferation in nasopharyngeal carcinoma cells

  2007cited by this paper
• Traffic safety for the cell: influence of cyclin-dependent kinase activity on genomic stability.

  2006cited by this paper
• Cyclin-dependent kinase pathways as targets for cancer treatment.

  2006cited by this paper
• Targeting Cyclins and Cyclin-Dependent Kinases in Cancer: Lessons from Mice, Hopes for Therapeutic Applications in Humans

  2006cited by this paper
• TNF-α enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B

  2006cited by this paper
• TNF-alpha enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B.

  2006cited by this paper
• Cyclin D1 overexpression induces epidermal growth factor-independent resistance to apoptosis linked to BCL-2 in human A431 carcinoma

  2006cited by this paper
• Regulation of Intracellular Cl- Concentration through Volume-regulated ClC-3 Chloride Channels in A10 Vascular Smooth Muscle Cells*

  2005cited by this paper
• Targeting the cell cycle: a new approach to cancer therapy.

  2005cited by this paper
• Prostate cancer and inositol hexaphosphate: efficacy and mechanisms.

  2005cited by this paper
• Cell cycle regulation and neural differentiation

  2003cited by this paper
• Molecular structure and physiological function of chloride channels.

  2002cited by this paper
• Phytochemicals as Cell Cycle Modulators A Less Toxic Approach in Halting Human Cancers

  2002cited by this paper
• Regulatory volume decrease is actively modulated during the cell cycle

  2002cited by this paper
• ClC-3 Is a Fundamental Molecular Component of Volume-sensitive Outwardly Rectifying Cl− Channels and Volume Regulation in HeLa Cells and Xenopus laevis Oocytes*

  2002cited by this paper
• Functional inhibition of native volume‐sensitive outwardly rectifying anion channels in muscle cells and Xenopus oocytes by anti‐ClC‐3 antibody

  2001cited by this paper
• Hepatocellular carcinoma results from chronic cyclin D1 overexpression in transgenic mice.

  2001cited by this paper
• Differential expression of volume‐regulated anion channels during cell cycle progression of human cervical cancer cells

  2000cited by this paper
• The role of ClC‐3 in volume‐activated chloride currents and volume regulation in bovine epithelial cells demonstrated by antisense inhibition

  2000cited by this paper
• A NEW APPROACH TO CANCER THERAPY

  1959cited by this paper

• Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation

  2025cites this paper
• Targeting ion channels: innovative approaches to combat cancer drug resistance

  2025cites this paper
• Paclitaxel induces pyroptosis by inhibiting the volume‑sensitive chloride channel leucine‑rich repeat‑containing 8a in ovarian cancer cells

  2023cites this paper
• Circular RNA XRCC5 aggravates glioma progression by activating CLC3/SGK1 axis via recruiting IGF2BP2.

  2023cites this paper
• X-RAY MEASUREMENT OF INTRACELLULAR CHLORIDE AND OTHER IONS IN MAMMALIAN CELLS

  2023cites this paper
• Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers

  2023cites this paper
• Role of synaptotagmin 13 (SYT13) in promoting breast cancer and signaling pathways

  2023cites this paper
• Anti-Aging Effects of R-Phycocyanin from Porphyra haitanensis on HUVEC Cells and Drosophila melanogaster

  2022cites this paper
• SOX2 regulates paclitaxel resistance of A549 non-small cell lung cancer cells via promoting transcription of ClC-3

  2022cites this paper
• The Role of E3 Ligase Pirh2 in Disease

  2022cites this paper
• Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

  2021cites this paper
• lncRNA TPT1-AS1 knockdown inhibits liver cancer cell proliferation, migration and invasion

  2021cites this paper
• Iso-suillin-induced DNA damage leading to cell cycle arrest and apoptosis arised from p53 phosphorylation in A549 cells.

  2021cites this paper
• ClC-3 promotes paclitaxel resistance via modulating tubulins polymerization in ovarian cancer cells.

  2021cites this paper
• Osthole Alleviates Neointimal Hyperplasia in Balloon-Induced Arterial Wall Injury by Suppressing Vascular Smooth Muscle Cell Proliferation and Downregulating Cyclin D1/CDK4 and Cyclin E1/CDK2 Expression

  2021cites this paper
• Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.

  2020cites this paper
• SOX7 is involved in polyphyllin D-induced G0/G1 cell cycle arrest through down-regulation of cyclin D1

  2020cites this paper
• Upregulated Expression of TUBA1C Predicts Poor Prognosis and Promotes Oncogenesis in Pancreatic Ductal Adenocarcinoma via Regulating the Cell Cycle

  2020cites this paper
• Inhibitory Effect of Jatrorrhizine-Platinum(II) Complex on Prostate Cancer Cells via PI3K/AKT and STA3/JAK2 Phosphorylation Downregulation

  2020cites this paper
• Saturated Fatty Acids Promote Hepatocytic Senecence through Negative Regulation of miR-34a/Cyclin-dependent Kinase 6.

  2020cites this paper
• MBD2 Correlates with a Poor Prognosis and Tumor Progression in Renal Cell Carcinoma

  2020cites this paper
• CLC-3 and SOX2 regulate the cell cycle in DU145 cells

  2020cites this paper
• OTT_A_256226 10001..10012

  2020cites this paper
• Overexpression of chloride channel-3 (ClC-3) is associated with human cervical carcinoma development and prognosis

  2019cites this paper
• Downregulation of ENDOCAN in myeloid leukemia cells inhibits proliferation and promotes apoptosis by suppressing nuclear factor‑κB activity.

  2019cites this paper
• Cyclin-Dependent Kinase Inhibitor 3 Promoted Cell Proliferation by Driving Cell Cycle from G1 to S Phase in Esophageal Squamous Cell Carcinoma

  2019cites this paper
• Euphorbia factor L2 inhibits TGF-β-induced cell growth and migration of hepatocellular carcinoma through AKT/STAT3.

  2019cites this paper
• Starvation-induced autophagy is up-regulated via ROS-mediated ClC-3 chloride channel activation in the nasopharyngeal carcinoma cell line CNE-2Z.

  2019cites this paper
• Regulation of p53 in the red-eared slider (Trachemys scripta elegans) in response to salinity stress.

  2019cites this paper
• LASS2 inhibits proliferation and induces apoptosis in HepG2 cells by affecting mitochondrial dynamics, the cell cycle and the nuclear factor‑κB pathways.

  2019cites this paper
• Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling

  2018cites this paper
• Activation of ClC‐3 chloride channel by 17β‐estradiol relies on the estrogen receptor α expression in breast cancer

  2018cites this paper
• Curcumin suppresses gastric cancer biological activity by regulation of miRNA-21: an in vitro study.

  2018cites this paper
• Inhibitory effects of Schisandrin B on human prostate cancer cells.

  2018cites this paper
• Chloride channel‐3 mediates multidrug resistance of cancer by upregulating P‐glycoprotein expression

  2018cites this paper
• High expression of leucine-rich repeat-containing 8A is indicative of a worse outcome of colon cancer patients by enhancing cancer cell growth and metastasis

  2018cites this paper
• Recombinant SjP40 protein enhances p27 promoter expression in hepatic stellate cells via an E2F1-dependent mechanism

  2017cites this paper
• High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation

  2017cites this paper
• Targeting cleavage and polyadenylation specific factor 1 via shRNA inhibits cell proliferation in human ovarian cancer

  2017cites this paper
• Restoration of microRNA-373 suppresses growth of human T-cell lymphoma cells by repressing CCND1.

  2016cites this paper