Abstract
The impact of Actin beta-like 2 (ACTBL2), a novel described actin isoform, on epithelial ovarian cancer (EOC) biology has not been investigated so far. In this study, we analyzed the prognostic and functional significance of ACTBL2 and its regulatory element Nuclear factor of activated T-cells 5 (NFAT5). The expression of ACTBL2 and NFAT5 was examined in tissue microarrays of 156 ovarian cancer patients by immunohistochemistry. Aiming to assess the molecular impact of ACTBL2 on cellular characteristics, functional assays were executed in vitro upon siRNA knockdown of ACTBL2 and NFAT5. ACTBL2 expression was identified as an independent negative prognostic factor for overall survival of EOC patients. EOC cell lines showed a significantly increased mRNA and protein level of ACTBL2 compared to the benign control. In vitro analyses upon siRNA knockdown of ACTBL2 displayed a significantly reduced cellular viability, proliferation and migration. siRNA knockdown of NFAT5 proved a significant molecular interplay by inducing a downregulation of ACTBL2 with a thus resulting concordant alteration in cellular functions, predominantly reflected in a decreased migratory potential of EOC cells. Our results provide significant evidence on the negative prognostic impact of ACTBL2 in EOC, suggesting its crucial importance in ovarian carcinogenesis by modulating cellular motility and proliferation.
Highlights
Epithelial ovarian cancer (EOC) is the fifth leading lethal tumor entity in women and the most common cause of death among gynecological cancer patients [1]
To examine the role of Actin beta-like 2 (ACTBL2) in epithelial ovarian cancer, ACTBL2 expression was investigated in 156 specimens
Summarizing, our findings suggest that the downregulation of ACTBL2 results in a significant decrease in viability, proliferation and migration of ovarian cancer cells, inversely supporting our hypothesis regarding the cellular function of ACTBL2
Summary
Epithelial ovarian cancer (EOC) is the fifth leading lethal tumor entity in women and the most common cause of death among gynecological cancer patients [1]. First-line therapy consists of cytoreductive surgery and adjuvant platinum-based chemotherapy in the clinical course. This is followed by the use of bevacizumab or poly-ADPribose-polymerase inhibitors, as a recent promising therapeutic approach in the maintenance treatment of patients with at least partial response to chemotherapy [7, 8]. While other gynecological tumor entities such as endometrial and cervical cancer are comparably prone to respond to immune therapy, no promising prognostic benefit in terms of ovarian cancer treatment has been shown yet [9,10,11,12]. Despite new emerging therapeutic strategies in the past few years, widely accepted and reliable biomarkers for ovarian cancer are still rare due to lacking profound knowledge on molecular pathological mechanisms enhancing tumor development and progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
