LAUSR

Simple Summary Colorectal cancer (CRC) is associated with high incidence and poor prognosis globally. An expression profile has revealed that circ_RNF13 is upregulated in CRC tumor samples. The aim of this study is to unravel the biological function and regulatory mechanism of circ_RNF13 in CRC. Circ_RNF13 stabilized TRIM24 via suppressing FBXW7-mediated degradation, thereby upregulating DDX27 expression in a TRIM24-dependent manner. The circ_RNF13/TRIM24/DDX27 axis is implicated in the regulation of stemness and chemoresistance in CRC. These findings identified promising prognostic biomarkers and novel targets for CRC chemotherapy. Abstract Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high incidence and poor prognosis worldwide. Circ_RNF13 is upregulated in CRC; however, the biological roles and downstream signaling of circ_RNF13 remain undefined. Methods: The characterization of circ_RNF13 was determined by Sanger sequencing, qRT-PCR, subcellular fractionation assay, and RNA FISH. Western blot analysis and qRT-PCR were employed to detect the expression of the key molecules and stemness markers in CRC tumor samples and cells. The stem-like activities of CRC cells were assessed by sphere formation assay, flow cytometry, and immunofluorescence (IF). Cell viability was monitored by CCK-8 assay. The chemosensitivity of CRC cells was assessed by colony formation and cell apoptosis assays. Bioinformatics analysis, RIP assay, RNA pull-down assay, and FISH/IF staining were used to detect the association between circ_RNF13 and TRIM24. The transcriptional regulation of DDX27 was investigated by ChIP assay, and the post-translational regulation of TRIM24 was detected by Co-IP. The in vitro findings were verified in a xenograft model. Results: circ_RNF13 and DDX27 were elevated in CRC tumor samples and cells. Knockdown of circ_RNF13 or DDX27 inhibited stemness and increased chemosensitivity in CRC cells. Mechanistically, circ_RNF13 regulated DDX27 expression via TRIM24-mediated transcriptional regulation, and circ_RNF13 stabilized TRIM24 via suppressing FBXW7-mediated TRIM24 degradation. In vivo studies revealed that the knockdown of circ_RNF13 impaired stemness and enhanced the chemosensitivity of CRC in the xenograft model. Conclusion: circ_RNF13 regulated the stemness and chemosensitivity of CRC by transcriptional regulation of DDX27 mediated by TRIM24 stabilization.