RAD51AP1 Promote Progression of Ovarian Cancer via TGF-β/Smad Signaling Pathway

Background: Ovarian cancer (OC) is one of the leading causes of female deaths. However, the molecular pathogenesis of OC has still remained elusive. This study aimed to explore the potential genes associated with the progression of OC. Methods: In the current study, 3 datasets of OC were downloaded from the GEO database to identify hub genes. Somatic mutation data obtained from TCGA were used to analyze the mutation in OC. RNA-seq and clinical data of OC patients retrieved from TCGA were used to investigate the diagnostic and prognostic values of hub genes. A series of in-vitro assays were performed to indicate the function of hub genes and their possible mechanisms in OC. Findings: RAD51AP1 was found as a hub gene, which expression higher was mainly associated with poor survival in OC patients. High expression level of RAD51AP1 was closely associated with further mutations in OC. Nomogram demonstrated that RAD51AP1 increased the accuracy of the model. Calibration curves illustrated that the predictive capability of 8-year nomogram was better. The Harrell's concordance index (C-index) of the model was 0.76. Downregulation of RAD51AP1 suppressed proliferation, migration, and invasion capabilities of OC cells in vitro. Additionally, scatter plots showed that RAD51AP1 was positively correlated with genes in TGF-β/Smad signaling pathway. The above-mentioned results were validated by RT-qPCR and Western blotting. Interpretation: Upregulation of RAD51AP1 was closely associated with mutations in OC. RAD51AP1 might represent an indicator for predicting OS of OC patients. Besides, RAD51AP1 could accelerate progression of OC by TGF-β/Smad signaling pathway. Funding Statement: This work was supported by National Natural Science Foundation of China (Grant/Award Numbers: 81672838 China), The Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (No.XMLX201705) and Beijing Municipal Science & Technology Commission No.Z181100001718193. Declaration of Interests: The authors stated that they "do not have anything to disclose regarding conflict of interest with respect to this manuscript." Ethics Approval Statement: Not required.