Long noncoding RNA BANCR promotes lymphangiogenesis and lymph node metastasis of pancreatic carcinoma by regulating VEGF-C/VEGFR-3 signaling pathway

Abstract

Abstract Background Long noncoding RNAs ( lncRNAs) have proved to play important roles in the tumorigenesis and development of pancreatic carcinoma (PC). The aim of our study is to investigate the expression of long noncoding BRAF-activated noncoding RNA (BANCR) and its role in PC lymph node metastasis. Methods BANCR expression was detected in PC tissues by using Real-time quantitative PCR (RT-qPCR). The correlation between BANCR expression and lymph node metastasis was analyzed. Immunofluorescence staining was used to determine microlymphatic vessel density (MLVD) of peritumoral tissues. The correlation between MLVD and lymph node metastasis and the association between BANCR expression and MLVD were also analyzed. VEGF-C and VEGFR-3 expressions in PC cells were detected by western blot in vitro, and the regulatory role of BANCR on VEGF-C/VEGFR-3 was identified by cell transfection techniques. The transfected PC cells were co-cultured with human lymphatic endothelial cells (HLECs) and the MLVD was detected by the magnification inverted fluorescence microscope. Results BANCR expression was remarkably increased in PC tissues, especially in the lymph node metastasis group (P < 0.0001). MLVD of the PC tissues in the lymph node metastasis group was significantly higher than the group without lymph node metastasis (P < 0.0001). The BANCR expression level significantly correlated with MLVD (P < 0.05). The result was further verified in PC cell lines. Depletion of BANCR inhibits lymphangiogenesis and down regulates VEGF-C/VEGFR-3 (P < 0.05). However, Overexpression of VEGF-C could counteract the inhibitory effect of siBANCR on lymphangiogenesis. Conclusions BANCR promotes lymphangiogenesis and lymph node metastasis of PC by regulating the VEGF-C /VEGFR-3 signaling pathway.