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Differential effects of the LncRNA RNF157-AS1 on epithelial ovarian cancer cells through suppression of DIRAS3- and ULK1-mediated autophagy
Analyses of several databases showed that the lncRNA RNF157 Antisense RNA 1 (RNF157-AS1) is overexpressed in epithelial ovarian cancer (EOC) tissues. In our study, suppressing RNF157-AS1 strikingly reduced the proliferation, invasion, and migration of EOC cells compared with control cells, while ove...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941098/ https://www.ncbi.nlm.nih.gov/pubmed/36805591 http://dx.doi.org/10.1038/s41419-023-05668-5 |
Sumario: | Analyses of several databases showed that the lncRNA RNF157 Antisense RNA 1 (RNF157-AS1) is overexpressed in epithelial ovarian cancer (EOC) tissues. In our study, suppressing RNF157-AS1 strikingly reduced the proliferation, invasion, and migration of EOC cells compared with control cells, while overexpressing RNF157-AS1 greatly increased these effects. By RNA pulldown assays, RNA binding protein immunoprecipitation (RIP) assays, and mass spectrometry, RNF157-AS1 was further found to be able to bind to the HMGA1 and EZH2 proteins. Chromatin immunoprecipitation (ChIP) assays showed that RNF157-AS1 and HMGA1 bound to the ULK1 promoter and prevented the expression of ULK1. Additionally, RNF157-AS1 interacted with EZH2 to bind to the DIRAS3 promoter and diminish DIRAS3 expression. ULK1 and DIRAS3 were found to be essential for autophagy. Combination autophagy inhibitor and RNF157-AS1 overexpression or knockdown, a change in the LC3 II/I ratio was found using immunofluorescence (IF) staining and western blot (WB) analysis. The autophagy level also was confirmed by autophagy/cytotoxicity dual staining. However, the majority of advanced EOC patients require platinum-based chemotherapy, since autophagy is a cellular catabolic response to cell stress. As a result, RNF157-AS1 increased EOC cell sensitivity to chemotherapy and death under cis-platinum (DDP) treatment by suppressing autophagy, as confirmed by cell count Kit-8 (CCK8) assays, flow cytometry, and autophagy/cytotoxicity dual staining. Therefore, the OS and PPS times were longer in EOC patients with elevated RNF157-AS1 expression. RNF157-AS1-mediated autophagy has potential clinical significance in DDP chemotherapy for EOC patients. |
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