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SMALL INTERFERING RNA TO GANKYRIN AS A POTENTIAL TOOL FOR
GLIOBLASTOMA THERAPY

Glioblastoma multiforme (GBM) is one of the most aggressive and invasive tumors with poor prognosis. Despite the intensive progress in development of new diagnostic and therapeutic drugs, the 5-year survival rate of patients with GBM is less than 5-10%. Search of new targets for therapy is promising approach for glioma therapy that will help to inhibit tumor growth, as well as increase the sensitivity of cancer cells to chemotherapy. Gankyrin is an oncogenic protein and a promising target for mono- and combination therapy of gliomas (Xu Guo et al, 2020). In this work, we have shown that the mRNA level of gankyrin is increased up to 10-15 times in primary human glioblastoma lines. Also, an increased mRNA level of gankyrin is associated with a negative methylation status of the o-methyl-guanine-DNA methyltransferase (MGMT) promoter, a biomarker of increased chemoresistance of tumor cells. Inhibition of gankyrin may become a promising tool for glioma therapy and opportunity to increase sensitivity of tumor cells to anticancer drugs. For this purpose, we synthesized small interfering RNA (siRNA) to gankyrin and formulated siRNA-lipid nanoparticles by mixing siRNA and lipids using a microfluidic device, performed physicochemical characterization. We demonstrated that obtained nanoparticles can effectively inhibit mRNA level of gankyrin in human glioblastoma cells.