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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
Joint Authors
Zoni, Eugenio
Kruithof-de Julio, Marianna
Krebs, Markus
Behrmann, Christoph
Kalogirou, Charis
Sokolakis, Ioannis
Kneitz, Susanne
Rech, Anne
Schilling, Bastian
Kübler, Hubert
Spahn, Martin
Kneitz, Burkhard
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-14
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Krebs, Markus& Behrmann, Christoph& Kalogirou, Charis& Sokolakis, Ioannis& Kneitz, Susanne& Kruithof-de Julio, Marianna…[et al.]. 2019. miR-221 Augments TRAIL-Mediated Apoptosis in Prostate Cancer Cells by Inducing Endogenous TRAIL Expression and Targeting the Functional Repressors SOCS3 and PIK3R1. BioMed Research International،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1126723
Modern Language Association (MLA)
Krebs, Markus…[et al.]. miR-221 Augments TRAIL-Mediated Apoptosis in Prostate Cancer Cells by Inducing Endogenous TRAIL Expression and Targeting the Functional Repressors SOCS3 and PIK3R1. BioMed Research International No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1126723
American Medical Association (AMA)
Krebs, Markus& Behrmann, Christoph& Kalogirou, Charis& Sokolakis, Ioannis& Kneitz, Susanne& Kruithof-de Julio, Marianna…[et al.]. miR-221 Augments TRAIL-Mediated Apoptosis in Prostate Cancer Cells by Inducing Endogenous TRAIL Expression and Targeting the Functional Repressors SOCS3 and PIK3R1. BioMed Research International. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1126723
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1126723