lncRNA NR2F1-AS1 promotes breast cancer angiogenesis through activating IGF-1/IGF-1R/ERK pathway

Long non-coding RNAs (lncRNAs) take various effects in cancer mostly through sponging with microRNAs (miRNAs). lncRNA NR2F1-AS1 is found to promote tumour progression in hepatocellular carcinoma, endometrial cancer and thyroid cancer. However, the role of lncRNA NR2F1-AS1 in breast cancer angiogenesis remains unknown. In this study, we found lncRNA NR2F1-AS1 was positively related with CD31 and CD34 in breast cancer through Pearson's correlation analysis, while lncRNA NR2F1-AS1 transfection promoted human umbilical vascular endothelial cell (HUVEC) tube formation. In breast cancer cells, lncRNA NR2F1-AS1 enhanced the HUVEC proliferation, tube formation and migration ability through tumour-conditioned medium (TCM). In zebrafish model, lncRNA NR2F1-AS1 increased the breast cancer cell-related neo-vasculature and subsequently promoted the breast cancer cell metastasis. In mouse model, lncRNA NR2F1-AS1 promoted the tumour vessel formation, increased the micro vessel density (MVD) and then induced the growth of primary tumour. Mechanically, lncRNA NR2F1-AS1 increased insulin-like growth factor-1 (IGF-1) expression through sponging miRNA-338-3p in breast cancer cells and then activated the receptor of IGF-1 (IGF-1R) and extracellular signal-regulated kinase (ERK) pathway in HUVECs. These results indicated that lncRNA NR2F1-AS1 could promote breast cancer angiogenesis through IGF-1/IGF-1R/ERK pathway.