• AHMAD TARMIZI CHE HAS

      Articles written in Journal of Biosciences

    • Influence of nNav1.5 on MHC class I expression in breast cancer

      AHMAD HAFIZ MURTADHA IRFAN IRSYAD MOHD AZAHAR NUR AISHAH SHARUDIN AHMAD TARMIZI CHE HAS NOOR FATMAWATI MOKHTAR

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      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.

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