Abstract
Background: Highly Upregulated in Liver Cancer (HULC) has been shown to play a pro-carcinogenic role in various cancer types. However, the specific molecular mechanisms of HULC in colorectal cancer (CRC) remain unclear. This study aimed to investigate the interaction between HULC and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in CRC and its role in promoting cancer progression. Methods: We first assessed HULC expression levels in CRC patient tissues and adjacent normal tissues using RNA sequencing and fluorescence in situ hybridization (FISH). Functional assays, including cell proliferation, migration, and colony formation, were performed in CRC cell lines. To further explore the interaction between HULC and IGF2BP2, we conducted RNA immunoprecipitation (RIP), RNA pull-down, and immunofluorescence co-localization assays. Additionally, the role of HULC in CRC growth and metastasis was evaluated in vivo using a nude mouse xenograft model and a liver metastasis model. Results: Our results showed that HULC was significantly overexpressed in CRC tissues and cell lines, with high HULC expression correlating with poor patient prognosis. HULC knockdown significantly inhibited CRC cell proliferation, migration, and epithelial-mesenchymal transition (EMT), while its overexpression enhanced these processes. RNA pull-down and RIP assays confirmed a direct interaction between HULC and IGF2BP2. Further experiments demonstrated that IGF2BP2 could reverse the inhibitory effects of HULC knockdown on CRC cell proliferation and migration, restoring the expression of CDK4, N-cadherin, and Vimentin. In vivo experiments revealed that HULC knockdown inhibited tumor growth and liver metastasis in nude mice, while HULC overexpression promoted malignant progression. Conclusion: HULC promotes CRC cell proliferation, migration, and EMT through its interaction with IGF2BP2, highlighting the critical role of the HULC-IGF2BP2 axis in CRC progression. These findings identify HULC as a potential molecular target for CRC treatment and offer new insights for therapeutic strategies targeting CRC patients.