Fig. 7
circPLPP4 acts as a therapy target in EOC pre-clinical models. A Schematic treatment administration (in vivo-optimized circPLPP4 inhibitor or control) in PDX models. B Representative images of circPLPP4 ISH analysis of OC tissue samples from OC patients. C, D Tumor weight and volume were examined in PDX-2 after 4-week treatment. E Tumor volumes were measured at the indicated time points in PDX-2. F, G Tumor weight and volume were assessed in PDX-1 after 4-week treatment. H Tumor volumes were measured at the indicated time points in PDX-1. I, J Body weights of tumor-bearing mice (PDX-1 and PDX-2) treated with CDDP combined with in vivo-optimized circPLPP4 inhibitor or control. K-M Decreased PIK3R1 (K), increased γ-H2AX level (L) and apoptosis (M) were showed in PDX-2 tumors after CDDP combined with in vivo-optimized circPLPP4 inhibitor treatment. Left, representative images of indicated staining. Right, quantification result according to its corresponding criteria . N Representative images showing high or low expression of circPLPP4, METTL3, IGF2BP1 and PIK3R1 in OC tumor specimens. O Correlation between circPLPP4 and METTL3 IGF2BP1or PIK3R1 in 166 OC tumor specimens. P qRT-PCR and western blotting analysis of circPLPP4 and METTL3, IGF2BP1 or PIK3R1 expression in five OC tumor specimens. circPLPP4 levels were normalized to that circPLPP4 expression of case 1. GAPDH was acted as loading controls. Q Graphical abstract for circPLPP4 function in CDDP resistance in OC. METTL3-mediated m6A modification for circPLPP4 acts as a sponge for miR-136 to promote OC CDDP resistance via regulating PIK3R1 signaling. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns indicates no significance