• Fulltext

       

        Click here to view fulltext PDF


      Permanent link:
      https://www.ias.ac.in/article/fulltext/jbsc/046/0070

    • Keywords

       

      Breast cancer; nNav1.5; MHC class I; APM; metastasis; invasion

    • Abstract

       

      Cancer metastasis occurs due to the ability of the tumour to evade immune recognition and response by alteringthe major histocompatibility complex class I (MHC class I). A comprehensive understanding of the MHC classI alteration in breast cancer metastasis is vital for the rational design and improvement of immunotherapies foradvanced cancer. In this study, we associate it with the elevation of ‘neonatal’ Nav1.5 (nNav1.5) mRNAexpression in the aggressive type of human breast cancer cells. Using real-time PCR, lower expression of TAP1(by - 4.83-fold), which is a part of the MHC class I antigen processing machinery (APM) pathway component,in contrast to the greater expression of nNav1.5 (by 3.76-fold), along with other metastatic markers,MMP1 (by 57.48-fold) and fibronectin (by 2.88-fold) in aggressive human breast cancer cell line, MDA-MB-231 were obtained. Subsequent knockdown of nNav1.5 (by 52.6%) in MDA-MB-231 via siRNA-SCN5Aresulted in downregulation of another metastatic marker, fibronectin (by 52.9%) but importantly, rescued MHCclass I expression (by 347% or 3.47-fold). Furthermore, the siRNA-SCN5A transfected cells failed to form aunified spheroid and incapable of efficiently invading the surrounding invasion matrix. In summary, theinfluence of nNav1.5 in regulating MHC class I mRNA expression to allow for breast cancer invasion isdemonstrated, supporting the potential of nNav1.5 as an immunotherapy target to overcome tumour immuneevasion thus preventing metastasis.

    • Author Affiliations

       

      AHMAD HAFIZ MURTADHA1 IRFAN IRSYAD MOHD AZAHAR1 NUR AISHAH SHARUDIN1 AHMAD TARMIZI CHE HAS2 NOOR FATMAWATI MOKHTAR1

      1. Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
      2. Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
    • Dates

       
    • Supplementary Material

       
  • Journal of Biosciences | News

    • Editorial Note on Continuous Article Publication

      Posted on July 25, 2019

      Click here for Editorial Note on CAP Mode

© 2021-2022 Indian Academy of Sciences, Bengaluru.