Th17 cells target the metabolic miR‐142‐5p–succinate dehydrogenase subunit C/D (SDHC/SDHD) axis, promoting invasiveness and progression of cervical cancers
| Title: | Th17 cells target the metabolic miR‐142‐5p–succinate dehydrogenase subunit C/D (SDHC/SDHD) axis, promoting invasiveness and progression of cervical cancers |
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| Authors: | Maike Pohlers, Selina Gies, Tanja Taenzer, Russalina Stroeder, Laura Theobald, Nicole Ludwig, Yoo‐Jin Kim, Rainer Maria Bohle, Erich Franz Solomayer, Eckart Meese, Martin Hart, Barbara Walch‐Rückheim |
| Source: | Molecular Oncology, Vol 18, Iss 9, Pp 2157-2178 (2024) |
| Publisher Information: | Wiley, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | cervical cancers, metastases, miR‐142‐5p, succinate dehydrogenase complex, T‐helper‐17 cells, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients. We previously demonstrated that Th17 cells are associated with therapy resistance as well as cervical cancer metastases and relapse; however, the underlying Th17‐driven mechanisms are not fully understood. Here, using microarrays, we found that Th17 cells induced an epithelial‐to‐mesenchymal transition (EMT) phenotype of cervical cancer cells and promoted migration and invasion of 2D cultures and 3D spheroids via induction of microRNA miR‐142‐5p. As the responsible mechanism, we identified the subunits C and D of the succinate dehydrogenase (SDH) complex as new targets of miR‐142‐5p and provided evidence that Th17–miR‐142‐5p‐dependent reduced expression of SDHC and SDHD mediated enhanced migration and invasion of cancer cells using small interfering RNAs (siRNAs) for SDHC and SDHD, and miR‐142‐5p inhibitors. Consistently, patients exhibited high levels of succinate in their serum associated with lymph node metastases and diminished expression of SDHD in patient biopsies correlated with increased numbers of Th17 cells. Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4+ T cells > 43.90% in situ was associated with reduced recurrence‐free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote cervical cancer progression and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1878-0261 1574-7891 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.13546 |
| Access URL: | https://doaj.org/article/f428a7b9ddb34a2188fd9525ee1f3e6c |
| Accession Number: | edsdoj.f428a7b9ddb34a2188fd9525ee1f3e6c |
| Database: | Directory of Open Access Journals |
| ISSN: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13546 |
| Published in: | Molecular Oncology |
| Language: | English |