• Users Online: 255
  • Print this page
  • Email this page
ORIGINAL ARTICLE
Year : 2019  |  Volume : 2  |  Issue : 1  |  Page : 46-54

Evidence of calcium-activated potassium channel subunit alpha-1 as a key promoter of glioma growth and tumorigenicity


1 Department of Molecular Oncology, Scintilla Academy for Applied Sciences' Education and Research, Bengaluru, Karnataka, India
2 Department of Molecular Oncology, Scintilla Academy for Applied Sciences' Education and Research; Department of Molecular Oncology, Scintilla Bio-MARC Pvt. Ltd., Bengaluru, Karnataka, India

Correspondence Address:
Dr. Nagendra Ningaraj
Scintilla Academy for Applied Sciences' Education and Research, Bengaluru - 560 060, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_44_18

Rights and Permissions

Background and Aim: Mechanisms of glioma progression are poorly understood. Upregulation of calcium-activated potassium channel subunit alpha-1 (KCNMA1), which encodes the α-subunit of maxi-calcium-activated potassium (BKCa) channels, is shown to be a novel mechanism for the malignant phenotype of brain tumor cells. The aim of this study was to establish the functional role of KCNMA1 in glioma biology. Materials and Methods: U-87-MG (U-87) cells were transfected to increase BKCa channel expression and activity. Glioma cell proliferation, invasiveness, and transendothelial migration were then measured. BKCa channels were blocked with iberiotoxin or short hairpin RNA (shRNA), which significantly inhibited K+ currents and growth of U-87 cells. It was tested whether KCNMA1 overexpression enhanced tumorogenecity in glioma xenograft mouse models by injecting wild-type and KCNMA1- overexpressing U87-MG cells. In parallel experiment, it was studied whether shRNA KCNMA1-expressing U-87 cells show attenuated glioma growth in mice. The study protocol was approved by the Institutional Animal Care and Use Committee, Mercer University (A0706007_01), Atlanta, GA, USA on July 20, 2007. Results: The effect of KCNMA1 overexpression in glioma growth as well as on associated cell biology functions such as proliferation, invasion, and migration was presented in this study. Messenger RNA and protein analyses revealed that KCNMA1 was amplified in 90% of high-grade gliomas and in high-grade glioma cell line U-87. In contrast, KCNMA1 amplification was not found in normal brain tissues. These data indicate that KCNMA1 plays critical role in glioma biology by interacting with several cellular processes. The data demonstrate that KCNMA1 amplification drives glioma cell proliferation and growth, which can be attenuated by its downregulation. Conclusion: KCNMA1 is a regulator of glioma cell proliferation and growth and thus qualifies as a promising diagnostic and therapeutic target in the treatment of glioma.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed3072    
    Printed188    
    Emailed0    
    PDF Downloaded230    
    Comments [Add]    
    Cited by others 2    

Recommend this journal