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miR-221 Augments TRAIL-mediated apoptosis in prostate cancer cells by inducing endogenous TRAIL expression and targeting the functional repressors SOCS3 and PIK3R1

Please always quote using this URN: urn:nbn:de:bvb:20-opus-202480
  • miR-221 is regarded as an oncogene in many malignancies, and miR-221-mediated resistance towards TRAIL was one of the first oncogenic roles shown for this small noncoding RNA. In contrast, miR-221 is downregulated in prostate cancer (PCa), thereby implying a tumour suppressive function. By using proliferation and apoptosis assays, we show a novel feature of miR-221 in PCa cells: instead of inducing TRAIL resistance, miR-221 sensitized cells towards TRAIL-induced proliferation inhibition and apoptosis induction. Partially responsible for thismiR-221 is regarded as an oncogene in many malignancies, and miR-221-mediated resistance towards TRAIL was one of the first oncogenic roles shown for this small noncoding RNA. In contrast, miR-221 is downregulated in prostate cancer (PCa), thereby implying a tumour suppressive function. By using proliferation and apoptosis assays, we show a novel feature of miR-221 in PCa cells: instead of inducing TRAIL resistance, miR-221 sensitized cells towards TRAIL-induced proliferation inhibition and apoptosis induction. Partially responsible for this effect was the interferon-mediated gene signature, which among other things contained an endogenous overexpression of the TRAIL encoding gene TNFSF10. This TRAIL-friendly environment was provoked by downregulation of the established miR-221 target gene SOCS3. Moreover, we introduced PIK3R1 as a target gene of miR-221 in PCa cells. Proliferation assays showed that siRNA-mediated downregulation of SOCS3 and PIK3R1 mimicked the effect of miR-221 on TRAIL sensitivity. Finally, Western blotting experiments confirmed lower amounts of phospho-Akt after siRNA-mediated downregulation of PIK3R1 in PC3 cells. Our results further support the tumour suppressing role of miR-221 in PCa, since it sensitises PCa cells towards TRAIL by regulating the expression of the oncogenes SOCS3 and PIK3R1. Given the TRAIL-inhibiting effect of miR-221 in various cancer entities, our results suggest that the influence of miR-221 on TRAIL-mediated apoptosis is highly context- and entity-dependent.show moreshow less

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Metadaten
Author: Markus Krebs, Christoph Behrmann, Charis Kalogirou, Ioannis Sokolakis, Susanne Kneitz, Marianna Kruithof-de Julio, Eugenio Zoni, Anne Rech, Bastian Schilling, Hubert Kübler, Martin Spahn, Burkhard Kneitz
URN:urn:nbn:de:bvb:20-opus-202480
Document Type:Journal article
Faculties:Medizinische Fakultät / Urologische Klinik und Poliklinik
Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Language:English
Parent Title (English):BioMed Research International
Year of Completion:2019
Volume:2019
Pagenumber:6392748
Source:BioMed Research International (2019) 2019:6392748. https://doi.org/10.1155/2019/6392748
DOI:https://doi.org/10.1155/2019/6392748
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Cancer Cell
Release Date:2020/05/14
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2019
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International