Abstract
Long non-coding RNA RAD51 antisense RNA 1 (RAD51-AS1, also known as TODRA) has been shown to be down-regulated by E2F1, a key cell cycle and apoptosis regulator, in breast cancer. Little is known regarding the role of RAD51-AS1 in disease. Here, we investigate the role of RAD51-AS1 in epithelial ovarian cancer (EOC). Using luciferase reporter and chromatin immunoprecipitation experiments, we verified RAD51-AS1 as a target of E2F1 under negative regulation in EOC. We then examined RAD51-AS1 expression in EOC samples using in situ hybridization (ISH). RAD51-AS1 was localized to the nucleus and found to be a critical marker for clinical features that significantly correlated with poor survival in EOC patients. RAD51-AS1 was also an independent prognostic factor for EOC. Overexpression of RAD51-AS1 promoted EOC cell proliferation, while silencing of RAD51-AS1 inhibited EOC cell proliferation, delayed cell cycle progression and promoted apoptosis in vitro and in vivo. RAD51-AS1 may participate in carcinogenesis via regulation of p53 and p53-related genes. Our study highlights the role of RAD51-AS1 as a prognostic marker of EOC. Based on its regulation of the tumor suppressor p53, RAD51-AS1-based therapy may represent a viable therapeutic option for EOC in the near future.
Highlights
Epithelial ovarian cancer (EOC) accounts for over 90% of all ovarian malignancies and is the most lethal gynecologic malignancy[1]
We designed ten pairs of primers, which cover 3 Kb upstream of Open Reading Frame of RAD51-AS1, and we found the putative binding site of E2F1 might located at 564–825 bp upstream of the Open Reading Frame of RAD51-AS1, a sequence in RAD51 intron 1 (Supplementary Fig. S1B)
We examined the effect of E2F1 on RAD51-AS1 promoter activity in SKOV3. ip and HO8910 cells
Summary
Epithelial ovarian cancer (EOC) accounts for over 90% of all ovarian malignancies and is the most lethal gynecologic malignancy[1]. This fact is largely due to the advanced stage and frequent metastasis at diagnosis in most patients[2]. Finding optimal prognostic markers and therapeutic agents for ovarian cancer patients is necessary to improve disease outcomes. Understanding of the molecular mechanisms of cancer development and may facilitate the identification of biomarkers or therapeutic targets to improve patient outcomes. RAD51-AS1, a target gene of E2F1, may be involved in the regulation of cell cycle or apoptosis and participate in ovarian cancer development. Because little is known regarding the function of RAD51-AS1, the main aim of this study was to elucidate the role of RAD51-AS1 in EOC progression
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