Fig. 6. The feedback profile of PANDAR–SFRS2–p53 in ovarian cancer patients with chemoresistance and recurrence.

a QRT-PCR quantification of PANDAR expression in tissues from ovarian cancer patients collected at newly diagnosed stage (Sensitive) and after disease progression during platinum-based therapy (Resistance). P53 missense mutation is in accord with post-surgical pathology reports. Data presents the mean ± S.D. n = 7 patients determined by Student’s t-test. ***p < 0.001, ns, non-significant, p53 mutation, positive mutant-p53 more than 80%. b LNA ISH analysis of lncRNA PANDAR with LNA probes and IHC assay of SFRS2 protein with SFRS2 antibody in matched ovarian cancer tissues before platinum-based therapy (Sensitive) and after disease progression during platinum-based treatment (Resistance). Representative LNA ISH and IHC images are shown. Scrambled groups serve as negative controls. U6 groups serve as positive controls. Black arrow head indicates the positive expression of RNA or protein. Scale bar: 50 μm. c, d Representative images of p53-Ser15 (c) and PUMA (d) immunofluorescent staining on tissues from patients at platinum-sensitive stage and after platinum-resistant ovarian cancer diagnosis. Scale bar: 50 µm. Data presents the mean ± S.D. n = 10 independent fields per group determined by Student’s t-test. **p < 0.01, ***p < 0.001. e Schematic model of underlying mechanisms regarding cisplatin resistance. With the sequential stimulation of cisplatin, a certain amount of p53-dependent PANDAR is upregulated to interact with SFRS2, leading to a reduction of p53 and its phosphorylation at Ser15, which in turn inactivated p53-mediated genes expression, such as PUMA, BAX, NOXA, Mdm2, and downregulated subsequent apoptosis