Glioblastoma stem cells after RNF8 overexpression

RNF8 is downregulated in glioblastoma and low RNF8 expression correlates with poor patient prognosis. Overexpression (OE) of RNF8 in glioblastoma stem cell (GSC) impairs its proliferation and tumorigenicity, and the anti-cancer effects of RNF8 are dependent on both its FHA and RING domains. Paradoxically, transcriptomic analysis of RNF8 OE GSC reveals cell cycle as the top upregulated pathway. Mechanistically, RNF8 interacts with the mitotic checkpoint protein MAD2 in a RING domain-dependent manner to induce spindle assembly checkpoint (SAC) activation. RNF8 OE GSC displays increase level of aneuploidy and micronuclei formation, suggesting that RNF8 promotes chromosomal instability (CIN) in GSC through persistent SAC activation. Overall design: TS543 cells were transduced with either GFP vector or GFP RNF8 overexpression construct.