Abstract
Dysregulated expression of circular RNAs (circRNAs) has been implicated in the initiation and progression of various diseases, including cancer. In this study, we investigated the role of hsa_circ_0005571 in modulating the biological characteristics of colorectal cancer (CRC) cells. Initially, the circRNA expression profiles of CRC tissues and corresponding normal tissues were analyzed using bioinformatics to identify differentially expressed circRNAs. Subsequently, quantitative real-time PCR (qRT‒PCR) was used to validate the expression levels of hsa_circ_0005571 in both CRC tissues and cell lines. In vitro assays, including the Cell Counting Kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, wound healing, and Transwell invasion assays, were employed to assess the effects of hsa_circ_0005571 on CRC cell proliferation and invasion. Additionally, tumorigenic potential was examined through in vivo tumorigenesis experiments in nude mice. Bioinformatic predictions and experimental evidence indicated that hsa_circ_0005571 may function as a sponge for miR-520f-3p, which was found to be downregulated in CRC cells. Moreover, LRP8 was predicted and confirmed as a direct downstream target of miR-520f-3p, with both the mRNA and protein levels of LRP8 significantly elevated in CRC cells. Overall, our results suggest that hsa_circ_0005571 enhances CRC proliferation and invasion by modulating the miR-520f-3p/LRP8 axis. Furthermore, elevated hsa_circ_0005571 expression in CRC tissue samples and cell lines relative to that in normal controls was positively correlated with metastasis (p = 0.029) and advanced clinical stage (p = 0.006). Survival analyses revealed that CRC patients with high levels of hsa_circ_0005571 expression had significantly lower overall survival rates than did those with low expression (p < 0.05). Functional assays confirmed that hsa_circ_0005571 facilitates CRC cell proliferation and migration, whereas its knockdown results in reduced migration, proliferation, and tumorigenic potential in vivo. Finally, Western blot analyses demonstrated that LRP8 expression varied in accordance with the levels of hsa_circ_0005571 and miR-520f-3p, further confirming the involvement of the hsa_circ_0005571/miR-520f-3p/LRP8 regulatory axis in CRC. Our study suggested that hsa_circRNA_0005571 promotes proliferation and migration through the miR-520f-3p/LRP8 axis in CRC. Consequently, hsa_circ_0005571 may represent a promising novel gene target for the diagnosis and treatment of CRC.