MCPIP1 contributes to clear cell renal cell carcinomas development

• DOI: 10.1007/s10456-017-9540-2
• Publication Date: 2017-02-14T09:38:59Z
• 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
• Keywords: Hypoxia-Inducible Factors; Monocyte; Proinflammatory cytokine

Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes regulating stability of transcripts coding for proinflammatory cytokines controlling activity transcription factors, such NF-κB AP1. We found that MCPIP1 transcript levels are strongly downregulated in clear cell renal carcinoma (ccRCC) samples, which were derived from patients surgically treated cancer compared to surrounded normal tissues. Using Caki-1 cells a model, we analyzed role development. showed expression depends on proteasome activity; however, hypoxia inducible factor 2 alfa (HIF2α) key factors lowering expression. Furthermore, negatively regulates HIF1α HIF2α case last one, mechanism based regulation half time HIF2α. Enhanced results downregulation encoding VEGFA, GLUT1, IL-6. decreases mTOR kinase B (Akt) normoxic conditions. Taken together, contributes ccRCC