Fig 1: Kaplan–Meier survival analysis of overall survival according to clinicopathological characteristics.Notes: The overall survival curve of our enrolled cohort was shown (A). Patients’ age (B) and pathological grade (C) had no prognostic significance. Patients with advanced FIGO stages (D) and lower CA-125 levels (E) showed better overall survival. In addition, lower PTPL1 protein expression level was identified as an unfavorable prognostic factor by univariate analysis (F). *p<0.05.Abbreviations: CA-125, cancer antigen 125; PTPL1, protein tyrosine phosphatase L1.
Fig 2: Identification of I?Ba-pY42 as a novel site recognized by PTPL1.Notes: (A) Both PTPL1 and I?Ba were predominantly localized in the cytoplasm. Importantly, I?Ba-Y42 phosphorylation level was negatively correlated with the PTPL1 level. (B) In OV-90 cells transfected with PTPL1 plasmids, the phosphorylation on I?Ba-Y42 was lower than that in control cells, which was consistent with the data from clinical samples. Subsequently, the phosphorylated I?Ba protein underwent degradation, thereby released the NF-?B into the cell nucleus, as reflected by Western blot. By conducting the proliferation (C) and invasion (D) experiments, we found that the tumor-promoting effects of PTPL1-silencing were attenuated by I?Ba inhibitor Bay 11-7085 or its tyrosine-alanine (Y42A) mutation. (E) The signaling axis of PTPL1-I?Ba-pY42-NF-?B is shown in a schematic model. *p<0.05.Abbreviation: PTPL1, protein tyrosine phosphatase L1.
Fig 3: Effects of PTPL1 on tumor cell proliferation and invasion.Notes: (A) PTPL1 showed detectable expression level in both POC cells and OV-90 cells, although significantly lower than that in normal FTEC. (B) MTT assay revealed a tumor-promoting effect of silencing PTPL1, whereas PTPL1 overexpression attenuated cell proliferation. (C) Transfected OV-90 cells were subjected to Matrigel-Transwell assay, and an approximately 70% decrease was observed in PTPL1-overexpressing cells. Data are presented as mean ± SD. *P<0.05.Abbreviations: FTEC, fallopian tube epithelium cells; POC, primary ovarian cancer; PTPL1, protein tyrosine phosphatase L1.
Fig 4: Expression patterns and cellular localization of PTPL1 in ovarian carcinoma tissues and normal ovarian tissues.Notes: (A) The mRNA level of PTPL1 in HGSOC was significantly lower than that in adjacent NT tissues (P=0.042). (B) The protein expression of PTPL1 was compared in seven paired fresh-frozen HGSOC (T) and NT tissues by Western blot, five of them (5/7, 71.4%) showed higher levels in adjacent tissues. (C) Representative images of positive PTPL1 immunohistochemical staining in adjacent ovarian tissues, showing the localization of PTPL1 in the cell cytoplasm. (D) Representative negative-staining images were demonstrated in HGSOC tissues. Magnification: ×400. *P<0.05.Abbreviations: HGSOC, high-grade serous ovarian cancer; NT, nontumorous; PTPL1, protein tyrosine phosphatase L1.
Fig 5: PTPN13 was identified as a direct target of miR-30e. (A) The main target genes of miR-30e in cancer tissues. (B) Diagrams showed the miR-30e putative binding sites and corresponding mutant sites of PTPN13. (C) The expression level of PTPN13 was examined after transfection with miR-30e by real-time PCR and Western blotting assays. (D) Luciferase activity was detected after miR-30e transfection. (E) The expression level of PTPN13 was examined after transfection with sh-miR-30e by real-time PCR and Western blotting assays. *P < 0.05, **P < 0.01.
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