Affiliation:
1. Zhejiang University School of Medicine
2. Women's Hospital, Zhejiang University
Abstract
Abstract
Background
Epithelial ovarian cancer (EOC) is a highly prevalent disease that rapidly metastasizes and has poor prognosis. Most women are in the middle or late stages when diagnosed and have low survival rates. Recently, long non-coding RNAs (lncRNAs) were recognized to play pivotal roles in the development of EOC.
Methods
The expression of SLC25A21-AS1 and PTBP3 in EOC cells was assessed via qPCR. The proliferation activity of these cells was detected by EdU and CCK8 assays, while the death rate of apoptotic cells and the cell cycle were detected by flow cytometry. Detection of cell transfer rate by Transwell assay. Protein expression was measured through Western immunoblotting. Interactions between SLC25A21-AS1 and PTBP3 were detected through RNA immunoprecipitation (RIP), IF-FISH co-localization experiments and Electrophoretic mobility shift assay (EMSA).The in vivo importance of SLC25A21-AS1 as a tumor suppressor modulator was assessed using murine xenograft models.
Results
The lncRNA SLC25A21-AS1 has negligible expression in ovarian cancer tissues compared with that in normal ovarian tissues. A series of functional tests revealed that the upregulation of SLC25A21-AS1 markedly blocked the proliferation and metastasis of EOC cells in vitro, while its downregulation had the opposite effect. Overexpression of SLC25A21-AS1 in a nude mouse model of EOC in vivo resulted in slower tumor growth and weakened metastatic potential. Moreover, SLC25A21-AS1 reduced the protein stability of PTBP3 and promoted its degradation. Subsequent ubiquitination experiments confirmed that SLC25A21-AS1 acts on PTBP3 through the ubiquitin–proteasome pathway and binds to PTBP3 to exert its proteolytic effect, thereby inhibiting EOC cell proliferation and metastasis.
Conclusions
Our research reveals the effect of SLC25A21-AS1 in EOC development and suggests it can serve as a prognostic target by promoting the degradation of PTBP3 to improve patient survival.
Publisher
Research Square Platform LLC