Platelet-activating Factor Acetyl Hydrolase IB2 Dysregulated Cell Proliferation in Ovarian Cancer

Abstract BackgroundOvarian cancer is the world’s largest cause of death for gynaecologic diseases. Platelet-activating factor acetyl hydrolase IB2 (PAF-AH IB2) is an intracellular serine esterase that hydrolyzes platelet-activating factor, a G-protein-like trimer with two catalytic subunits and one regulatory subunit. The deregulatory role of PAF-AHIB2 in the etiology of ovarian cancer is poorly understood. MethodsIn this study, the TCGA exploration and cancer tissue immunohistochemistry were utilized to investigate aberrant overexpression of PAF-AH IB2 in ovarian cancer. PAF-AH IB2 Stable knocking down (KD) ovarian cancer cells were established to investigate the impact on the cell proliferation, migration, and tumorigenicity in vitro. The whole transcription profiling, tyrosine kinase profiling and standard cell functional assays were integrated to explore the biological importance and mechanism of PAF-AH IB2 modulated in ovarian cancer. ResultsInteresting, PAF-AH IB2 was identified significantly overexpression in four subtypes of ovarian cancer. PAF-AHIB2 KD significantly reduced cancer cell proliferation, migration, and tumorigenicity in vitro, activated Caspases and caused cell cycle arrest, and making the cells more sensitive to PAF. Several key regulators of multiple tyrosine kinases-mediated signaling pathway were down-regulated in PAF-AH 1B2 KD cells, revealing a novel interaction network between the growth factor receptors pathway and PAF-AH 1B2 mediated PAF signalling.Conclusions These results discovered an unrevealed role for PAFAH IB2 as a novel potential therapy target and essential signaling mediators in ovarian cancer pathogenesis, as well as new potential preventive and therapeutic strategies to inhibit this enzyme in clinical treatment for ovarian cancer.