APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progression
Renowned as the predominant form of kidney cancer, clear cell renal cell carcinoma (ccRCC) exhibits susceptibility to immunotherapies due to its specific expression profile as well as notable immune cell infiltration. Despite this, effectively treating metastatic ccRCC remains a significant challeng...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13721 |
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| _version_ | 1841556024425709568 |
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| author | Nora Hase Danny Misiak Helge Taubert Stefan Hüttelmaier Michael Gekle Marcel Köhn |
| author_facet | Nora Hase Danny Misiak Helge Taubert Stefan Hüttelmaier Michael Gekle Marcel Köhn |
| author_sort | Nora Hase |
| collection | DOAJ |
| description | Renowned as the predominant form of kidney cancer, clear cell renal cell carcinoma (ccRCC) exhibits susceptibility to immunotherapies due to its specific expression profile as well as notable immune cell infiltration. Despite this, effectively treating metastatic ccRCC remains a significant challenge, necessitating a more profound comprehension of the underlying molecular mechanisms governing its progression. Here, we unveil that the enhanced expression of the RNA‐binding protein DNA dC → dU‐editing enzyme APOBEC‐3C (APOBEC3C; also known as A3C) in ccRCC tissue and ccRCC‐derived cell lines serves as a catalyst for tumor growth by amplifying nuclear factor‐kappa B (NF‐κB) activity. By employing RNA‐sequencing and cell‐based assays in ccRCC‐derived cell lines, we determined that A3C is a stress‐responsive factor and crucial for cell survival. Furthermore, we identified that A3C binds and potentially stabilizes messenger RNAs (mRNAs) encoding positive regulators of the NF‐κB pathway. Upon A3C depletion, essential subunits of the NF‐κB family are abnormally restrained in the cytoplasm, leading to deregulation of NF‐κB target genes. Our study illuminates the pivotal role of A3C in promoting ccRCC tumor development, positioning it as a prospective target for future therapeutic strategies. |
| format | Article |
| id | doaj-art-16a1e25f157747e3a1fe6fc76fb00a63 |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-16a1e25f157747e3a1fe6fc76fb00a632025-01-07T14:42:32ZengWileyMolecular Oncology1574-78911878-02612025-01-0119111413210.1002/1878-0261.13721APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progressionNora Hase0Danny Misiak1Helge Taubert2Stefan Hüttelmaier3Michael Gekle4Marcel Köhn5Junior Group ‘Non‐Coding RNAs and RBPs in Human Diseases’, Medical Faculty Martin Luther University Halle/Wittenberg GermanySection for Molecular Cell Biology, Institute of Molecular Medicine Martin Luther University Halle/Wittenberg GermanyDepartment of Urology and Pediatric Urology University Hospital Erlangen, Friedrich Alexander University Erlangen/Nürnberg GermanySection for Molecular Cell Biology, Institute of Molecular Medicine Martin Luther University Halle/Wittenberg GermanyJulius‐Bernstein‐Institute of Physiology Martin Luther University Halle/Wittenberg GermanyJunior Group ‘Non‐Coding RNAs and RBPs in Human Diseases’, Medical Faculty Martin Luther University Halle/Wittenberg GermanyRenowned as the predominant form of kidney cancer, clear cell renal cell carcinoma (ccRCC) exhibits susceptibility to immunotherapies due to its specific expression profile as well as notable immune cell infiltration. Despite this, effectively treating metastatic ccRCC remains a significant challenge, necessitating a more profound comprehension of the underlying molecular mechanisms governing its progression. Here, we unveil that the enhanced expression of the RNA‐binding protein DNA dC → dU‐editing enzyme APOBEC‐3C (APOBEC3C; also known as A3C) in ccRCC tissue and ccRCC‐derived cell lines serves as a catalyst for tumor growth by amplifying nuclear factor‐kappa B (NF‐κB) activity. By employing RNA‐sequencing and cell‐based assays in ccRCC‐derived cell lines, we determined that A3C is a stress‐responsive factor and crucial for cell survival. Furthermore, we identified that A3C binds and potentially stabilizes messenger RNAs (mRNAs) encoding positive regulators of the NF‐κB pathway. Upon A3C depletion, essential subunits of the NF‐κB family are abnormally restrained in the cytoplasm, leading to deregulation of NF‐κB target genes. Our study illuminates the pivotal role of A3C in promoting ccRCC tumor development, positioning it as a prospective target for future therapeutic strategies.https://doi.org/10.1002/1878-0261.13721APOBEC3CccRCCNF‐κBRBP |
| spellingShingle | Nora Hase Danny Misiak Helge Taubert Stefan Hüttelmaier Michael Gekle Marcel Köhn APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progression Molecular Oncology APOBEC3C ccRCC NF‐κB RBP |
| title | APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progression |
| title_full | APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progression |
| title_fullStr | APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progression |
| title_full_unstemmed | APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progression |
| title_short | APOBEC3C‐mediated NF‐κB activation enhances clear cell renal cell carcinoma progression |
| title_sort | apobec3c mediated nf κb activation enhances clear cell renal cell carcinoma progression |
| topic | APOBEC3C ccRCC NF‐κB RBP |
| url | https://doi.org/10.1002/1878-0261.13721 |
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