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Published on: August 2, 2024
CircATRNL1 and circZNF608 Inhibit Ovarian Cancer by Sequestering miR-152-5p and Encoding Protein
Mengmeng Lyu1, Xiujuan Li2, Yang Shen1
1Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China.
Abstract:
Background: CircRNAs have been found to be involved in the pathogenesis of various diseases. We aimed to explore the roles of circRNAs in ovarian cancer. Methods: The expression levels of circRNAs in ovarian cancer and normal ovarian tissues were analyzed using RNA sequencing. Fluorescent in situ hybridization (FISH), proliferation assays and transwell assays were used to assess the effects of circRNAs on ovarian cancer. Results: CircATRNL1 and circZNF608 were downregulated in 20 ovarian cancer tissues compared to normal tissues. CircATRNL1 and circZNF608 are mainly located in the cytoplasm of ovarian cancer cells, and circATRNL1 is a highly conserved circRNA. The overexpression of circATRNL1 and circZNF608 inhibits the proliferation and invasion of ovarian cancer cells. We predicted miRNA-circRNA interactions for circZNF608 and circATRNL1 and obtained 63 interactions. However, a luciferase reporter assay showed that only miR-152-5p was sequestered by circZNF608. Bioinformatics analysis and experiments indicated that circATRNL1 contains an internal ribosome entry site and an open reading frame encoding a 131 aa protein. Conclusion: In conclusion, circATRNL1 and circZNF608 are two downregulated circRNAs in ovarian cancer and work as tumor suppressors. CircZNF608 may exert antitumor activity in ovarian cancer by binding miR-152-5p, and circATRNL1 may encode a 131 aa protein.
Insights
Two circular RNAs, circATRNL1 and circZNF608, are downregulated in ovarian cancer and act as tumor suppressors. CircZNF608 inhibits cancer by binding miR-152-5p, while circATRNL1 may encode a protein.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in various disease pathologies.
- Their specific roles in ovarian cancer pathogenesis require further elucidation.
Purpose of the Study:
- To investigate the expression and function of circRNAs in ovarian cancer.
- To identify specific circRNAs involved in ovarian cancer development and progression.
Main Methods:
- RNA sequencing to analyze circRNA expression in ovarian cancer tissues versus normal tissues.
- Fluorescent in situ hybridization (FISH), proliferation, and Transwell assays to assess circRNA function.
- Luciferase reporter assays to validate miRNA-circRNA interactions.
Main Results:
- CircATRNL1 and circZNF608 were found to be significantly downregulated in ovarian cancer tissues.
- Overexpression of circATRNL1 and circZNF608 suppressed ovarian cancer cell proliferation and invasion.
- CircZNF608 directly interacts with miR-152-5p, and circATRNL1 potentially encodes a 131 amino acid protein.
Conclusions:
- CircATRNL1 and circZNF608 function as tumor suppressors in ovarian cancer.
- CircZNF608's antitumor effects may be mediated through its interaction with miR-152-5p.
- CircATRNL1's potential to encode a protein warrants further investigation into its functional mechanisms.
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