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Angiogenesis
Published in: Angiogenesis 3/2017

Open Access 01-08-2017 | Original Paper

MCPIP1 contributes to clear cell renal cell carcinomas development

Authors: Janusz Ligeza, Paulina Marona, Natalia Gach, Barbara Lipert, Katarzyna Miekus, Waclaw Wilk, Janusz Jaszczynski, Andrzej Stelmach, Agnieszka Loboda, Jozef Dulak, Wojciech Branicki, Janusz Rys, Jolanta Jura

Published in: Angiogenesis | Issue 3/2017

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Abstract

Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development.
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Metadata
Title
MCPIP1 contributes to clear cell renal cell carcinomas development
Authors
Janusz Ligeza
Paulina Marona
Natalia Gach
Barbara Lipert
Katarzyna Miekus
Waclaw Wilk
Janusz Jaszczynski
Andrzej Stelmach
Agnieszka Loboda
Jozef Dulak
Wojciech Branicki
Janusz Rys
Jolanta Jura
Publication date
01-08-2017
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 3/2017
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-017-9540-2

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