Part:BBa_K4469008

miRNA-28

miRNA28 is known to be a tumor suppressor of hepatocellular carcinoma and have hampered expression in HCC. It is also an inhibitor of N4BP1 (Cornel et al., 2020; Shi & Teng, 2015). N4BP1 prohibits the activation of NFkB by competitive binding for polyubiquitin with NEMO (Nepravishta et al., 2019). Inhibition of NFkB results in downregulation of MHC class I molecules (Forloni et al., 2010). Therefore, it is decided to include the miR 28-5p in the viral vector because of its antagonistic ability of N4BP1, aiming to upregulate NFkB and hence the MHC class I expression (Cornel et al., 2020). In addition, according to an open-access database, liver cancer cells show strong positivity of N4BP1 expression, indicating that miR 28-5p is likely to be working in hepatocellular carcinoma.

Reference

Cornel, A. M., Mimpen, I. L., & Nierkens, S. (2020). MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy. Cancers, 12(7), 1760. https://doi.org/10.3390/cancers12071760

Forterre, A., Komuro, H., Aminova, S., & Harada, M. (2020). A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies. Cancers, 12(7), 1852. https://doi.org/10.3390/cancers12071852

Nepravishta, R., Ferrentino, F., Mandaliti, W., Mattioni, A., Weber, J., Polo, S., Castagnoli, L., Cesareni, G., Paci, M., & Santonico, E. (2019). CoCUN, a Novel Ubiquitin Binding Domain Identified in N4BP1. Biomolecules, 9(7), 284. https://doi.org/10.3390/biom9070284

Shi, X., & Teng, F. (2015). Down-regulated Mir-28-5p in human hepatocellular carcinoma correlated with tumor proliferation and migration by targeting insulin-like growth factor-1 (IGF-1). Molecular and Cellular Biochemistry, 408(1-2), 283–293. https://doi.org/10.1007/s11010-015-2506-z