Downregulation of ALDH5A1 Promotes Tumor Metastasis and Contributes to Poor Prognosis in Ovarian Cancer

Abstract Background Despite modern therapies, ovarian cancer (OC) remains a major clinical problem with a high risk of mortality. We previously reported that low expression of ALDH5A1 could serve as an indicator for predicting poor prognosis in OC. However, the function of ALDH5A1 in OC progression has not been elucidated yet. Methods We firstly compared ALDH5A1 expression in metastatic tissues to primary site of OC based on the Oncomine database. Then wound healing assay and Transwell assay were utilized to determine the biological role of OC cells transfected with ALDH5A1 siRNA. To unravel the potential mechanism of ALDH5A1 meditating metastasis of OC, the co-expression profile of ALDH5A1 in OC cell lines and OC patients were generated using cBioPortal. Moreover, qRT-PCR and WB analysis were used to detect the expression levels of metastasis-related genes after ALDH5A1 suppression, HPA database was used to confirm the relative expression of ALDH5A1 and MMP in OC patients. In addition, KM survival plots in 578 OC patients from the TCGA database were analyzed. Results We proved lower ALDH5A1 expression in metastatic tissues compared to primary site of OC, and knockdown of ALDH5A1 promoted the malignant behavior of OC cells. Additionally, the co-expression profile of ALDH5A1 was significantly enriched in extracellular matrix (ECM) organization pathway. We further confirmed ALDH5A1 was negatively associated with MMP expression in OC, indicating that ALDH5A1 was closely related to OC metastasis via ECM organization pathway. Finally, KM survival plots revealed that low ALDH5A1 expression contributed to poor OC survival. Conclusions These results suggested a key role of ALDH5A1 in driving the progression of OC and identified ALDH5A1 as a robust therapeutic target of OC.