Fig. 6
Targeting circRNA-SORE in vivo retards sorafenib-resistant HCC. a In vivo luminescent imaging of orthotopically implanted SKhep1-SR-luc or SKhep1-SR-luc-sh-cricRNA-SORE cells in 4–6 week-old male BALB/c nude mice treated with solvent or sorafenib (30 mg/kg/day) for 4 weeks from the fourth week after implantation. Luminescence intensity ranges from low (blue) to high (red). Tumor burdens were quantified by total photon flux (p/s). b-d Flow Chart of LM3-CDX-SR model construction. The first CDX generation was constructed in 4–6 week-old male BALB/c nude mice and treated with sorafenib (30 mg/kg daily, oral gavage). Twelve weeks later, the most resistant xenograft was disaggregated and implanted subcutaneously into 4–6 week-old BALB/c nude mice as the second SR-CDX. Four weeks after implantation, the second SR-CDX mice were treated with sorafenib (30 mg/kg daily, oral gavage) and locally injected with sh-circRNA-SORE lentivirus or its negative control (twice a week for 2 weeks). Mice were euthanized on the sixth week and tumors were isolated and the tumor weights were measured. The subcutaneous tumor size was measured and recorded every 2 days using the Vernier caliper as follows: tumor volume (mm3) = (L × W2)/2, where L is the long axis and W the short axis. e Immunohistochemistry for Wnt2b and β-catenin comparing sh-circRNA-SORE and control CDX. Scale bar, 50 μm. f Hypothetical model for circRNA-SORE function in HCC. circRNA-SORE acts as a sponge for miR-103a-2-5p and miR-660-3p to promote HCC sorafenib resistance by regulating the Wnt2b/β-catenin signaling pathway