Suppression of CLC-3 chloride channel reduces the aggressiveness of glioma through inhibiting nuclear factor-κB pathway
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Bing Wang1,2,*, Jing Xie3,*, Hai-Yong He1,*, En-Wen Huang4, Qing-Hua Cao5, Lun Luo1, Yong-Shi Liao2 and Ying Guo1
1Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
2Department of Neurosurgery, The Second Affiliated Hospital, University of South China, Hengyang, China
3Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China
4Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
5Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
*These authors have contributed equally to this work
Ying Guo, email: [email protected]
Yong-Shi Liao, email: [email protected]
Keywords: CLC-3, glioma, invasion, nuclear factor-κB, matrix metalloproteinase
Received: March 17, 2017 Accepted: May 06, 2017 Published: July 08, 2017
CLC-3 chloride channel plays important roles on cell volume regulation, proliferation and migration in normal and cancer cells. Recent growing evidence supports a critical role of CLC-3 in glioma metastasis, however, the mechanism underlying is unclear. This study finds that CLC-3 is upregulated in glioma tissues and positively correlated with WHO histological grade. Patients with high CLC-3 expression had an overall shorter survival time, whereas patients with low expression of CLC-3 had a better survival time. Silencing endogenous CLC-3 with ShCLC-3 adenovirus significantly decreases volume-regulated chloride currents, inhibits the nuclear translocation of p65 subunit of Nuclear Factor-κB (NF-κB), decreases transcriptional activity of NF-κB, reduces MMP-3 and MMP-9 expression and decreases glioma cell migration and invasion. Taken together, these results suggest CLC-3 promotes the aggressiveness of glioma at least in part through nuclear factor-κB pathway, and might be a novel prognostic biomarker and therapeutic target for glioma.
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