Fig. 6.

Circ-EGFR knockdown enhanced the therapeutic effect of nimotuzumab in glioblastoma (GBM). (A). Neurosphere-forming capability in indicated cells. (B). Cell proliferation of the indicated groups was determined by CCK8. (C). The expression of EGFR downstream signaling was determined in each group. (D). Representative HE staining in each experimental group are shown. (E). Survival analysis was conducted with the Kaplan–Meier curve in indicated groups. (F). Illustration of circ-EGFR function. Normally, after activation by EGF, the ubiquitylated EGFR was followed by endocytosis and degradation. In brain tumor cells where rolling-translated EGFR (rtEGFR) was abundantly expressed, rtEGFR formed a complex with EGFR and prevented its endocytosis. This disrupted the normal downregulation of the EGFR, extended it signaling lifespan and promoted tumorigenesis. Lines show the mean ± SD. *P < .05, **P < .01, ***P < .001. Data are representative of 2–3 experiments with similar results.