The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation
Fangfang Jian1, Xiaoxia Che1,2, Jingjing Zhang1
1Department of obstetrics and gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Abstract:
Aberrant long-noncoding RNA (lncRNA) expression has been shown to be involved in the pathogenesis of endometrial cancer (EC). Herein, we report a novel tumor suppressor lncRNA SOCS2-AS1 in EC. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization and nuclear/cytoplasmic fractionation assays were used to detect the subcellular location. We found that SOCS2-AS1 was downregulated in EC tissues. Its reduced expression was correlated with advanced clinical stage and poor prognosis. Forced expression of SOCS2-AS1 suppressed EC cell proliferation and induced cell-cycle arrest and apoptosis. SOCS2-AS1-binding proteins were detected using RNA pull-down assay and mass spectrometry. Mechanistically, SOCS2-AS1 bound to Aurora kinase A (AURKA) and increased its degradation through the ubiquitin-proteasome pathway. In conclusion, SOCS2-AS1 may thus serve as a prognostic predictor and a biomarker for AURKA-inhibitor treatment in EC patients.
Insights
A novel tumor suppressor, long-noncoding RNA SOCS2-AS1, is downregulated in endometrial cancer (EC). Its reduced expression correlates with poor prognosis, and it targets Aurora kinase A (AURKA) for degradation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant long-noncoding RNA (lncRNA) expression is implicated in endometrial cancer (EC) pathogenesis.
- Identifying novel lncRNAs involved in EC is crucial for understanding disease mechanisms and developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of the lncRNA SOCS2-AS1 as a potential tumor suppressor in endometrial cancer.
- To elucidate the molecular mechanism underlying SOCS2-AS1's function in EC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess SOCS2-AS1 expression levels in EC tissues.
- In situ hybridization and subcellular fractionation to determine SOCS2-AS1 localization.
- RNA pull-down assay and mass spectrometry to identify SOCS2-AS1-binding proteins.
- Functional assays to evaluate the impact of SOCS2-AS1 on EC cell proliferation, cell cycle, and apoptosis.
Main Results:
- SOCS2-AS1 was significantly downregulated in EC tissues compared to normal tissues.
- Reduced SOCS2-AS1 expression correlated with advanced clinical stage and poorer patient prognosis.
- Overexpression of SOCS2-AS1 inhibited EC cell proliferation, induced cell-cycle arrest, and promoted apoptosis.
- SOCS2-AS1 was found to bind to Aurora kinase A (AURKA) and promote its degradation via the ubiquitin-proteasome pathway.
Conclusions:
- SOCS2-AS1 functions as a tumor suppressor in endometrial cancer.
- SOCS2-AS1 may serve as a valuable prognostic biomarker for EC patients.
- SOCS2-AS1 could be a potential therapeutic target or biomarker for AURKA-inhibitor treatments in EC.
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