Fig. 7: CircPLOD2a/b are highly expressed in GBM tissues and its downstream gene XIRP1 is correlated with glioma grade and prognosis.

A, B Relative expression of (A) circPLOD2a and (B) circPLOD2b were examined by qRT-PCR in clinical samples from patients with grade II-III (n = 10) and grade IV (n = 9) glioma. C Relative expression of XIRP1 in tissues from circPLOD2a-high and -low groups. The GBM tissues were divided into circPLOD2a-high (n = 10) and -low (n = 9) groups according to the expression of circPLOD2a. D Relative expression of XIRP1 in tissues from circPLOD2b-high and -low groups. The GBM tissues were divided into circPLOD2a-high (n = 10) and -low (n = 9) groups according to the expression of circPLOD2b. E Relative expression of XIRP1 in GBM and non-tumor brain tissues were analyzed from Rembrandt database. F Representative immunohistochemistry images of XIRP1 in a tissue microarray containing grade I (n = 3), II (n = 50), III (n = 24) and IV (n = 94) glioma. Scale bar: 100 μm. G, H Expression levels of XIRP1 in tissues from patients with different grade glioma were evaluated by (G) the percentage of cells with strong/moderate/weak intensity of XIRP1 staining and (H) histochemistry score (H-score) of each tissue on this microarray. I Kaplan–Meier survival curves of glioma patients in XIRP1-high and low groups. Glioma patients were categorized into XIRP1-high and -low group by the expression level of XIRP1 based on H-score. J Schematic illustration of HIF1α/circPLOD2a/b/HuR/XIRP1 axis. HIF1α induces the up-regulation of linear PLOD2, circPLOD2a and circPLOD2b under hypoxia. CircPLOD2a/b suppress XIRP1 by competitively binding to HuR and enhance GBM cell aggressiveness. Data are shown as mean ± SEM (error bars) and analyzed using Student’s t-test (A–E), ANOVA (H) and Log-rank test (I).