Suppression of CLC-3 chloride channel reduces the aggressiveness of glioma through inhibiting nuclear factor-?B pathway.

ABSTRACT: 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-?B (NF-?B), decreases transcriptional activity of NF-?B, 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-?B pathway, and might be a novel prognostic biomarker and therapeutic target for glioma.

SUBMITTER: Wang B 

PROVIDER: S-EPMC5609961 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature