Role of PP2A phosphatases and miR-19b in DNA damage response and temozolomide resistance of GBM tumours
|Director of thesis||Prof. Dr. Erik Vassella|
|Co-director of thesis|
|Summary of thesis||
The preliminary results from the group revealed that attenuation of miR-19b results in major changes in the phospho-proteome, enhances phosphatase activity and reduces efficiency in TMZ-induced DNA damage response in a GBM cell line. miR-19b is potentially able to target PP2A subunits PPP2R2A, PPP2R1B, PPP2R5A and PPP2R5E. PPP2R5E targeting by miR-19b was confirmed experimentally. Consistent with these findings, miR-19b levels were inversely correlated with the expression of PP2A subunits in GBM tissues, suggesting that miR-19b controls the expression of PP2A.
Specific aims of the ongoing project would be:
A) Analysis of PP2A and DNA damage response genes in tissues of TMZ resistant recurrent GBM cases.
B) Mechanistic analysis of PP2A and miR-19b in patient-derived GBM stem cells (GSCs).
C) Assess PP2A regulation by miR-19b
D) Assess if targeting miR-19b can be exploited for anti-GBM adjuvant therapy in an orthotopic mouse model.
|Administrative delay for the defence|