MCPIP1 Contributes to Clear Cell Renal Cell Carcinomas Development

Overview

Journal Angiogenesis

Publisher Springer

Specialty Hematology

Date 2017 Feb 16

PMID 28197812

Citations 34

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

Affiliations

Soon will be listed here.

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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