CircARHGAP10 inhibits colorectal cancer cell proliferation, migration and invasion by governing the miR-29a-5p/LPP axis and regulating Wnt/β-catenin signaling pathway.

CircARHGAP10 is significantly downregulated in colorectal cancer (CRC), but its functional role and underlying molecular mechanism in CRC progression remain unelucidated. Here, we first detected circARHGAP10 expression in CRC tissues and adjacent normal tissues, as well as in CRC cell lines and normal intestinal epithelial cells. Functional analyses using CCK-8, EdU, colony formation, wound healing, and transwell assays demonstrated that circARHGAP10 overexpression notably inhibits CRC cell proliferation, migration, and invasion, while circARHGAP10 knockdown promotes these malignant phenotypes. Mechanistically, bioinformatic predictions, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays confirmed that circARHGAP10 acts as a competing endogenous RNA (ceRNA) to sponge miR-29a-5p, thereby upregulating the expression of its downstream target gene LPP. Furthermore, we found that circARHGAP10 modulates LPP, the Wnt/β-catenin signaling pathway and reverses epithelial-mesenchymal transition (EMT) through the miR-29a-5p, as validated by rescue experiments. Collectively, our findings reveal that circARHGAP10 functions as a tumor suppressor in CRC via two independent regulatory branches downstream of the circARHGAP10/miR-29a-5p cascade. On one hand, it restores LPP expression to block the malignant proliferation, migration and invasion of CRC cells; on the other hand, this signaling cascade mitigates excessive Wnt/β-catenin pathway activation and reverses EMT. This newly identified circRNA-centered regulatory network provides a promising novel therapeutic target for CRC intervention.