Relationship of RSUME and HIF-1α/VEGFA pathways with invasion of pituitary adenoma / 肿瘤

ABSTRACT

Objective: To investigate the relationships of RWD-containing sumoylation enhancer (RSUME) and hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway with invasion of pituitary adenoma. Methods: The expression levels of RSUME, HIF-1α and VEGF-A mRNAs in human pituitary adenoma tissues were detected by real-time fluorescence quantitative-PCR. The expression levels of small ubiquitin-related modifier-1 (SUMO-1), HIF-1α and VEGF-A proteins in pituitary adenoma tissues were detected by Western blotting. After transfecting with small interfering RNA (siRNA)-targeting RSUME into murine pituitary adenoma AtT-20 cells, the expression levels of RSUME, HIF-1α and VEGF-A mRNAs as well as SUMO-1, HIF-1α and VEGF-A proteins were detected by real-time fluorescence quantitative-PCR and Western blotting, respectively. The invasion ability was measured by Transwell assay. Results: The expression levels of RSUME, HIF-1α and VEGF-A mRNAs as well as SUMO-1, HIF- 1α and VEGF-A proteins in invasive pituitary adenoma tissues were significantly higher than those in non-invasive pituitary adenoma tissues and normal pituitary tissues (all P < 0.05). The SUMO-1 expression was positively correlated with HIF-1α expression in invasive pituitary adenoma tissues (r = 0.687, P < 0.05), and HIF-1α expression was positively correlated with VEGF-A expression (r = 0.773, P < 0.05). The expression levels of RSUME and VEGF-A mRNAs as well as SUMO-1, HIF-1α and VEGF-A proteins in AtT-20 cells after transfection with RSUME siRNA were significantly lower than those in the negative control group (AtT-20 cells transfected with negative control siRNA) and the blank control group (AtT-20 cells without any transfection) (all P < 0.05). The invasion ability of AtT-20 cells after transfection with RSUME siRNA was significantly inhibited (P < 0.05). Conclusion: RSUME can promote the invasion of pituitary adenoma by regulating HIF-1α/VEGF pathway. Silencing of RSUME gene may inhibit the invasion of pituitary adenoma cells.