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doi:10.22028/D291-42808
Titel: | Th17 cells target the metabolic miR-142-5p-succinate dehydrogenase subunit C/D (SDHC/SDHD) axis, promoting invasiveness and progression of cervical cancers |
VerfasserIn: | Pohlers, Maike Gies, Selina Taenzer, Tanja Stroeder, Russalina Theobald, Laura Ludwig, Nicole Kim, Yoo-Jin Bohle, Rainer Maria Solomayer, Erich Franz Meese, Eckart Hart, Martin Walch-Rückheim, Barbara |
Sprache: | Englisch |
Titel: | Molecular Oncology |
Bandnummer: | 18 (2024) |
Heft: | 9 |
Seiten: | 2157-2178 |
Verlag/Plattform: | Wiley |
Erscheinungsjahr: | 2023 |
Freie Schlagwörter: | cervical cancers metastases miR-142-5p succinate dehydrogenase complex T-helper-17 cells |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | 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. |
DOI der Erstveröffentlichung: | 10.1002/1878-0261.13546 |
URL der Erstveröffentlichung: | https://doi.org/10.1002/1878-0261.13546 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-428080 hdl:20.500.11880/38385 http://dx.doi.org/10.22028/D291-42808 |
ISSN: | 1878-0261 1574-7891 |
Datum des Eintrags: | 9-Sep-2024 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0001-FigS1.pdf https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0002-FigS2.tif https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0003-FigS3.tif https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0004-FigS4.tif https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0005-FigS5.tif https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0006-FigS6.tif https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0007-FigS7.tif https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0008-TableS1.pdf https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0009-TableS2.pdf https://febs.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F1878-0261.13546&file=mol213546-sup-0010-TableS3.pdf |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Frauenheilkunde M - Humangenetik M - Infektionsmedizin M - Pathologie |
Professur: | M - Prof. Dr. Rainer M. Bohle M - Prof. Dr. Eckart Meese M - Prof. Dr. Sigrun Smola M - Prof. Dr. E.-F. Solomayer |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
---|---|---|---|---|
Molecular Oncology - 2023 - Pohlers - Th17 cells target the metabolic miR‐142‐5p succinate dehydrogenase subunit C D SDHC.pdf | 6,85 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons