LncRNA <i>LINC01503</i> promotes angiogenesis in colorectal cancer by regulating VEGFA expression <i>via</i> miR-342-3p and HSP60 binding

Colorectal cancer (CRC) ranks among the top five most common malignant tumors worldwide and has a high mortality rate. Angiogenesis plays an important role in CRC progression; however, anti-angiogenesis therapy still has many limitations. Long non-coding RNAs (lncRNAs) participate in tumor progression by regulating the expression of vascular endothelial growth factor in metastatic CRC. Thus, targeting specific lncRNAs may provide some new hope for anti-angiogenic strategies. Through analyzing data from both clinical samples and The Cancer Genome Atlas database, we found that the lncRNA <i>LINC01503</i> was specifically upregulated in CRC tissues and was associated with tumor progression and poor overall survival. We also demonstrated that <i>LINC01503</i> enhanced the capacity for tube formation and migration of vascular endothelial cells, thus promoting CRC tumorigenesis by upregulating vascular endothelial growth factor A (VEGFA) expression in CRC cells. Mechanistically, <i>LINC01503</i> promoted the expression of VEGFA by simultaneously regulating both mRNA and protein stability of VEGFA by binding to miR-342-3p and the chaperone HSP60, respectively. The upregulation of <i>LINC01503</i> in CRC cells was attributed to the CREB-binding protein CBP/p300-mediated H3K27 acetylation of the <i>LINC01503</i> promoter region. Taken together, our findings clarify the mechanism by which <i>LINC01503</i> may promote CRC angiogenesis, implying that <i>LINC01503</i> may serve as a potential prognostic biomarker and therapeutic target for CRC.