Yes-associated protein (YAP) promotes progression of glioma and poor prognosis of human

Abstract Background: Yes-associated protein(YAP) plays an important role in signal transduction and gene transcription regulation in 1 normal cells, with elevated and over-expressed YAP levels observed in various malignant tumors. The aim of this study was 2 to investigate the expression of YAP in malignant glioma, and to study the possible relationship of YAP expression with the 3 occurrence and development of malignant glioma. 4 Methods: Immunohistochemical staining was used to assess the expression of YAP and phosphor-YAP in malignant glioma 5 tissue and normal brain tissue, and their protein and mRNA levels were evaluated through Western blotting and reverse 6 transcription-polymerase chain reaction (RT-PCR), respectively. Normal brain tissue obtained from the functional lesion of 7 the epilepsy patients. After transfection of YAPsiRNA oligonucleotides or pcDNA3.1-hYAP plasmid, their effects on glioma 8 cells were investigated using western blot, cell proliferation, cycle, apoptosis and invasion, respectively. We conducted the 9 2 co-Immunoprecipitation to verify the combination of YAP and PPARγ, explore the mechanism of action. 10 Results: YAP-positive expression was found in 9 cases of normal brain and 60 cases of glioma. A significantly higher 11 expression of YAP in glioma tissue as compared with normal brain tissue at both protein and mRNA levels, and YAP proteins 12 mainly expressed and located in the nucleus and only a small percentage in the cytoplasm of glioma tissue. Phosphor-YAP 13 protein expression showed high staining of the cytoplasm, but no staining of the nuclear. While, with the enhancement of 14 the malignant degree, the cytoplasm YAP(p-YAP) expression is lower gradually than normal brain tissues. Further study in 15 glioma cell lines in which YAP was either overexpressed or depleted confirmed that YAP markedly promoted the cell 16 proliferation, cycle, invasion and inhibited the cell apoptosis. Moreover, YAP in company with PPARγ regulates the cell 17 proliferatin and effects the gliomagenesis. 18 Conclusion: These results indicate that YAP plays an important role in glioma and might be a useful therapeutic target of 19 glioma. 20