Correlation Between Rsume And RSUME、HIF-1α/VEGF-A Pathway And Invasion Of Pituitary Adenoma

Objective:To investigate the functions and correlation of small ubiquitin related modifiers-1(SUMO-1) of RWD containing sumoylation enhancer(RSUME) and hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) with pituitary adenoma. To explore the relationship of expression between RSUME, SUMO-1, HIF-1 and /VEGF in invasive pituitary adenoma with biological behavior, in order to anti angiogenesis, reduce the invasiveness of pituitary adenomas and provide a new theoretical basis. Methods:1. To investigate the correlation of expression between RSUME, SUMO-1, HIF-1α, VEGF-A in pituitary adenoma and the invasive pituitary adenomas.According to the Hardy-Wilson and K nosp standards and the exam of iconography and the intraoperative findings, pituitary adenomas is divided into invasive pituitary adenomas groups and non- invasive pituitary adenomas groups. The expression of protein and mRNA levels of RSUME, SUMO-1, HIF-1α, VEGF-A was detected by immunohistochemistry, western blot, qPCR in 49 cases of non- invasive pituitary adenoma, 34 cases of invasive pituitary adenomas and 9 normal pituitary capsule, and analysed the expression in different types of pituitary adenomas.2. To study the mechanism of RSUME and HIF-1α/VEGF-A pathway in pituitary adenomaAfter transfecting with siRNA-targeting RSUME into mouse pituitary adenoma AtT-20 cells, the expression levels of RSUME, HIF-1α, VEGF-A mRNAs and SUMO-1, HIF-1α and VEGF-A proteins were detected by real- time fluorescence quantitative-PCR and Western blotting, respectively. And then the invasion was measured by transwell assay. Results:1. Expression and correlation of RSUME, SUMO-1, HIF-1α, VEGF-A in pituitary adenoma(1) The expression levels of RSUME, HIF-1α, VEGF-A mRNAs and SUMO-1, HIF-1α, VEGF-A proteins in invasive pituitary adenoma tissues were significantly higher than those in non invasive pituitary adenoma tissues and normal pituitary tissues(2) The relationship between SUMO-1 and HIF-1α in invasive pituitary adenoma tissues was positive correlation(r=0.687, p<0.05), and the relationship between HIF-1α and VEGF-A was also positive correlation(r=0.773, p<0.05).2. Mechanism of RSUME and HIF-1α/VEGF pathway in pituitary adenoma(1) The mRNA expression levels of RSUME were raised obviously after cobalt chloride affected AtT-20 cells(p<0.05), but the mRN A expression levels of HIF-1α did not change significantly(p>0.05); The protein expression levels of RSUME, HIF-1α were raised obviously after cobalt chloride affected AtT-20 cells(p<0.05);(2) The expression levels of RSUME mRNA and protein after transfection with HIF-1α siRNA in AtT-20 cells did not change significantly(p>0.05);(3) The protein expression levels of HIF-1α were decreased significantly after transfection with RSUME siRNA in At T-20 cells(p<0.05), but the mRNA expression levels of HIF-1α did not change significantly(p>0.05);(4) The invasion inhibition rate in AtT-20 cell after transfection with RSUME siRNA were lower than that of the negative control group and blank control group. Conclusion:(1) The expression of RSUME, SUMO-1, HIF-1α, VEGF-A were significantly increased in invasive pituitary adenoma, and the correlation of the protein expression of SUMO-1 and HIF-1α/VEGF-A pathway was positive correlation;(2) RSUME can enhance the functions of HIF-1α/VEGF-A pathway, and promote the invasion of pituitary adenomas;(3) RSUME can be used as a molecular target to reduc e the invasiveness of pituitary adenomas.