Fig 2: AG490 treatment reverses the carcinogenic-inducing effects of PRP3 in benign epidermal keratinocyte cells. (A) The impact of AG490 treatment on the PRP3 mRNA expression. (B) AG490 treatment inhibited the activation of JAK2/STAT3 pathway in benign epidermal keratinocyte cells. (C) The relative protein expression of PRP3, phosphorylated JAK2 and phosphorylated STAT3. (D) The AG490 treatment suppressed the promoted effects of PRP3 on cell proliferation. (E) Colony formation assay revealed that the AG490 treatment inhibited the ability of colony formation. (F) Promoted effect of PRP3 on cell invasion were inhibited by treatment with AG490. (G) The analyze of the invaded cell number. (H) The ability of cell migration was explored via wound healing assay. **P < 0.01. EMT, epithelial-mesenchymal transition; PRP3, pre-mRNA processing factor 3.

Fig 3: Forced overexpression of STAT3 increased YAP protein, YAP mRNA and YAP signaling downstream CTGF and CYR61 mRNA expression in H146 and H446 cells. (A–E) The STAT3, p-STAT3 and YAP protein expression levels increased in STAT3-overexpressing H146 and H446 cells compared with control H146 and H446 cells. (F,G) The floating cell morphology was changed to an adherent cell morphology after STAT3 overexpression in H146 and H446 cells. (H,I) YAP, CTGF and CYR61 mRNA expression significantly increased in STAT3-overexpressing H146 and H446 cells compared with control H146 and H446 cells. (Error bars indicate standard deviations; *** p ≤ 0.001.)

Fig 4: Upregulation of PRP3 promoted cell viability and migration in a human benign epidermal keratinocyte cell line. (A) The effect of PRP3 on the JAK2/STAT3 pathway was investigated. (B) The relative protein expression of PRP3, phosphorylated JAK2 and phosphorylated STAT3. (C) The expression location of PRP3 was explored via immunofluorescence (D) CCK8 assay revealed that impact of PRP3 on cell proliferation. (E) Colony formation assay revealed that overexpression of PRP3 promoted cell viability. (F) Transwell assay was used to explore the impact of PRP3 on cell invasion. (G) The analyze of the invaded cell number. (H) The ability of cell migration was explored via wound healing assay. *P < 0.05, **P < 0.01. PRP3, pre-mRNA processing factor 3.

Fig 5: Carnosic acid enhances the sorafenib-induced reduction of P-ERK1/2 and P-STAT3 levels in HCC cells.Huh7 and HepG2 cells were treated with the indicated agents for 24 hours. The protein levels of P-ERK1/2 (Thr202/Tyr204), P-STAT3 (Tyr605), and total (T) ERK1/2 and STAT3 were determined by western blots. The ratios of P-ERK1/2 vs. T-ERK1/2 and P-STAT3 vs. T-STAT3 are shown in the table below. CA further enhances Sf-induced reduction of activation of both ERK1/2 and STAT3.