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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
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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



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