TY  - JOUR
A1  - Krebs, Markus
A1  - Behrmann, Christoph
A1  - Kalogirou, Charis
A1  - Sokolakis, Ioannis
A1  - Kneitz, Susanne
A1  - Kruithof-de Julio, Marianna
A1  - Zoni, Eugenio
A1  - Rech, Anne
A1  - Schilling, Bastian
A1  - Kübler, Hubert
A1  - Spahn, Martin
A1  - Kneitz, Burkhard
T1  - miR-221 Augments TRAIL-mediated apoptosis in prostate cancer cells by inducing endogenous TRAIL expression and targeting the functional repressors SOCS3 and PIK3R1
JF  - BioMed Research International
N2  - 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 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.
KW  - Cancer Cell
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202480
VL  - 2019
ER  - 
TY  - THES
A1  - Behrmann, Christoph
T1  - MicroRNA-221 sensitiviert Prostatakarzinomzellen gegenüber TRAIL durch Inhibition von SOCS-3 und PIK3R1
T1  - MicroRNA-221 sensitizes prostate cancer cells to TRAIL via inhibition of SOCS-3 and PIK3R1
N2  - MicroRNA-221 (miR-221) führt in Prostatakarzinomzellen zu einer Induktion einer TRAIL-supprotiven Signatur als Folge einer Interferonaktivierung mit Heraufregulation von STAT-1 und den TRAIL-relevanten, interferonsensitiven Genen TNFSF-10 und XAF-1. Ferner führt die Inhibierung des bekannten Zielgenes SOCS-3 sowie die Inhibierung des neu beschriebenen Zielgenens PIK3R1 zu einer TRAIL-Sensitivierung in den untersuchten Prostatakarzinomzellen.
N2  - MicroRNA-221 (miR-221) mediates TRAIL-sensitivation of prostate cancer cells via inducing an TRAIL-supportive signature. This was shown by upregulation of STAT-1 and the TRAIL inducing the interferone sensitive genes XAF-1 and TNFSF-10. Furthermore the inhibition of two miR-221 targets mediates TRAIL sensitivation. The inhibition of the known target SOCS-3 and the new target PIK3R1 both led to TRAIL sensitivation of prostate cancer cells.
KW  - microrna
KW  - Prostatakarzinom
KW  - tumor necrosis factor
KW  - microRNA-221
KW  - TRAIL
KW  - PIK3R1
KW  - SOCS-3
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199205
ER  -