LncRNA MANCR Acts as a ceRNA to Sponge MicroRNA-20a-5p and Upregulate GCNT4 to Suppress Angiogenesis in Colorectal Cancer.

BACKGROUND Colorectal cancer (CRC) is ranked among the most prevalent digestive system malignancies worldwide. Its progression is closely associated with angiogenesis, which not only supplies nutrients and oxygen to tumors but also facilitates metastasis. Dysregulation of lncRNA MANCR (MANCR) in multiple cancers influences tumorigenesis and development. However, the function and molecular mechanism of MANCR in CRC angiogenesis remain unclear. METHODS This study constructed a MANCR/miR-20a-5p/GCNT4 axis using TCGA, starBase, and TargetScan Human databases. Expression of MANCR, microRNA-20a-5p, and GCNT4 in CRC was analyzed using the TCGA database, with validation performed in cell lines. In vitro functional assays (CCK-8, colony formation, transwell migration/invasion, tube formation, and Western blotting) were conducted to evaluate the impact of MANCR on CRC cell proliferation, migration, invasion, and angiogenesis. Bioinformatics analysis was used to analyze the Pearson correlation between MANCR and microRNA-20a-5p, and between microRNA-20a-5p and GCNT4. Functional interactions of MANCR and microRNA-20a-5p, and ceRNA regulatory mechanisms were verified via dual-luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation, with further exploration of GCNT4's role in angiogenesis regulation conducted. RESULTS Significant downregulation of MANCR expression was observed in CRC tissues and cell lines. Overexpression of MANCR robustly inhibited CRC cell proliferation, migration, invasion, and angiogenesis. Significant negative correlations were observed between MANCR and microRNA-20a-5p, and between microRNA-20a-5p and GCNT4. MANCR sponged microRNA-20a-5p to downregulate its expression, while microRNA-20a-5p repressed GCNT4 expression by binding to the 3'UTR of GCNT4 mRNA. Overexpression of microRNA-20a-5p reversed MANCR-mediated suppression of angiogenesis. CONCLUSION LncRNA MANCR sponges microRNA-20a-5p, relieves the suppression of GCNT4 expression caused by microRNA-20a-5p, and elevates GCNT4 expression, ultimately inhibiting tumor growth and angiogenesis in CRC.