Long non-coding RNA RAD51-AS1 promotes the tumorigenesis of ovarian cancer by elevating EIF5A2 expression

• DOI: 10.1007/s00432-024-05671-z
• Publication Date: 2024-04-07T17:01:21Z
• Authors: Lu Zhao; Jia Huang; Wenting Liu; Xiaoyan Su; Bei Zhao; Xianggang Wang; Xiaoju He
• Keywords: Ovarian Neoplasms; 0303 health sciences; Carcinogenesis; Research; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Transformation, Neoplastic; Cell Movement; Cell Line, Tumor; Humans; Female; RNA, Long Noncoding; Rad51 Recombinase; Cell Proliferation

Abstract Purpose The present study aims to determine the molecular mechanism mediated by RAD51 antisense RNA 1 (RAD51-AS1) in ovarian cancer (OvCA).

Methods The data associated with RAD51-AS1 in OvCA were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Relative expression of RAD51-AS1 was detected. Determination of cell proliferation, metastasis, and invasion was performed by cell counting, colony formation, would-healing, and transwell invasion assays. Protein levels were detected by western blotting. The molecular mechanism mediated by RAD51-AS1 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assays. Subcutaneous tumorigenesis models were used to confirm the function of RAD51-AS1 in vivo.

Results Data from TCGA and GEO showed that RAD51-AS1 was associated with poor prognosis in OvCA patients and DNA repair, cell cycle, focal adhesion, and apoptosis in SKOV3.ip cells. High levels of RAD51-AS1 were detected in OvCA cells. Overexpressing RAD51-AS1 enhanced the proliferative, invading, and migratory capabilities of OvCA cells in vitro while silencing RAD51-AS1 exhibited the opposite effects. Mechanically, RAD51-AS1 elevated eukaryotic initiation factor 5A2 (EIF5A2) expression as a sponge for microRNA (miR)-140-3p. Finally, the role of RAD51-AS1 was verified by subcutaneous tumorigenesis models.

Conclusion RAD51-AS1 promoted OvCA progression by the regulation of the miR-140-3p/EIF5A2 axis, which illustrated the potential therapeutic target for OvCA.