A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7
Abstract Background Recently, prostate cancer (PCa) has been increasing in incidence and mortality, which seriously threatens men’s physical and mental health. Adenosine (A)-to-inosine (I) RNA editing, contributing to nearly 90% of all editing events in human, has been reported to contribute to path...
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| Format: | Article |
| Language: | English |
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Springer
2025-05-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02449-8 |
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| author | Shengyi Lin Hang Huang Yeping Li Yongyong Lu Tingyu Ye |
| author_facet | Shengyi Lin Hang Huang Yeping Li Yongyong Lu Tingyu Ye |
| author_sort | Shengyi Lin |
| collection | DOAJ |
| description | Abstract Background Recently, prostate cancer (PCa) has been increasing in incidence and mortality, which seriously threatens men’s physical and mental health. Adenosine (A)-to-inosine (I) RNA editing, contributing to nearly 90% of all editing events in human, has been reported to contribute to pathogenesis and progression of cancer. Here, we aimed to elaborate the role and mechanism of A-to-I-edited POLA2 in PCa. Methods RT-qPCR, Western blotting, and immunohistochemistry were used to assess gene expression. RNA editing levels were determined by Sanger sequencing. Colony formation, CCK-8, and Transwell assays were conducted to detect cell proliferation and metastasis. And Flow cytometry assay was applied to examine CD8+ T cell activity and tumor cell apoptosis. Dual-luciferase reporter assay demonstrated the relationship between gene and miRNA. The ability of glycolysis was measured by Seahorse XF96 Analyzer. Results A-to-I RNA overediting of POLA2 was identified in PCa patients, which was related to unfavorable clinical outcomes and prognosis. The A-to-I RNA editing of POLA2 was mediated by ADAR1 enzyme in human cancers. Functionally, A-to-I RNA editing endowed POLA2 with carcinogenicity in PCa development, and POLA2 overediting aggravated cell viability and metastasis of PCa. More importantly, POLA2 overediting fortified glycolysis and impaired CD8+ T cell cytotoxicity in PCa. Mechanically, edited POLA2 upregulates BTBD7 expression in PCa by binding to miR-596. Conclusion A-to-I RNA edited POLA2 attained carcinogenesis in PCa by impeding immune infiltration, fortifying glycolysis and upregulating BTBD7, indicating that edited POLA2 has the potential to become a tool for gene therapy. |
| format | Article |
| id | doaj-art-76b1b45ec9f94087991abe4b9f04559e |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-76b1b45ec9f94087991abe4b9f04559e2025-08-20T02:25:15ZengSpringerDiscover Oncology2730-60112025-05-0116111410.1007/s12672-025-02449-8A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7Shengyi Lin0Hang Huang1Yeping Li2Yongyong Lu3Tingyu Ye4Department of Urology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract Background Recently, prostate cancer (PCa) has been increasing in incidence and mortality, which seriously threatens men’s physical and mental health. Adenosine (A)-to-inosine (I) RNA editing, contributing to nearly 90% of all editing events in human, has been reported to contribute to pathogenesis and progression of cancer. Here, we aimed to elaborate the role and mechanism of A-to-I-edited POLA2 in PCa. Methods RT-qPCR, Western blotting, and immunohistochemistry were used to assess gene expression. RNA editing levels were determined by Sanger sequencing. Colony formation, CCK-8, and Transwell assays were conducted to detect cell proliferation and metastasis. And Flow cytometry assay was applied to examine CD8+ T cell activity and tumor cell apoptosis. Dual-luciferase reporter assay demonstrated the relationship between gene and miRNA. The ability of glycolysis was measured by Seahorse XF96 Analyzer. Results A-to-I RNA overediting of POLA2 was identified in PCa patients, which was related to unfavorable clinical outcomes and prognosis. The A-to-I RNA editing of POLA2 was mediated by ADAR1 enzyme in human cancers. Functionally, A-to-I RNA editing endowed POLA2 with carcinogenicity in PCa development, and POLA2 overediting aggravated cell viability and metastasis of PCa. More importantly, POLA2 overediting fortified glycolysis and impaired CD8+ T cell cytotoxicity in PCa. Mechanically, edited POLA2 upregulates BTBD7 expression in PCa by binding to miR-596. Conclusion A-to-I RNA edited POLA2 attained carcinogenesis in PCa by impeding immune infiltration, fortifying glycolysis and upregulating BTBD7, indicating that edited POLA2 has the potential to become a tool for gene therapy.https://doi.org/10.1007/s12672-025-02449-8A-to-I RNA editingPOLA2Prostatic cancerBTBD7Immune infiltrationGlycolysis |
| spellingShingle | Shengyi Lin Hang Huang Yeping Li Yongyong Lu Tingyu Ye A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7 Discover Oncology A-to-I RNA editing POLA2 Prostatic cancer BTBD7 Immune infiltration Glycolysis |
| title | A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7 |
| title_full | A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7 |
| title_fullStr | A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7 |
| title_full_unstemmed | A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7 |
| title_short | A-to-I RNA edited POLA2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating BTBD7 |
| title_sort | a to i rna edited pola2 attains carcinogenesis in prostatic cancer by impeding immune infiltration and upregulating btbd7 |
| topic | A-to-I RNA editing POLA2 Prostatic cancer BTBD7 Immune infiltration Glycolysis |
| url | https://doi.org/10.1007/s12672-025-02449-8 |
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