Circ_0057105 promotes intrahepatic cholangiocarcinoma progression by sponging miR-1290 and regulating the MDM2/P53...

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited treatment options, underscoring the need to identify new regulatory molecules. Through high-throughput sequencing of five paired ICC and adjacent normal tissues, we identified a significantly upregulated circular RNA, circ_0057105, which is further validated in ICC cell lines and clinical samples. A correlation between elevated circ_0057105 expression and poor prognosis in ICC patients was observed based on clinical data. Functional in vitro and in vivo assays demonstrated that circ_0057105 promotes ICC cell proliferation, migration, and invasion. Mechanistically, circ_0057105 functions as a competing endogenous RNA (ceRNA) that sponges miR-1290, leading to the upregulation of MDM2. This subsequently enhances MDM2-mediated ubiquitination and degradation of the tumor suppressor p53, thereby inhibiting the p53 signaling pathway. Furthermore, in vivo delivery of small interfering RNA targeting circ_0057105 (si-circ_0057105) encapsulated in lipid nanoparticles (LNPs) effectively suppressed its expression and showed promising therapeutic efficacy. In conclusion, our study demonstrates that circ_0057105 drives ICC progression via the miR-1290-MDM2-p53 axis, establishing it as a valuable prognostic biomarker and a promising therapeutic target. The delivery of siRNA targeting circ_0057105 via lipid nanoparticles represents a potential translational strategy.