SIRT2 - JAK1 Etkileşimi Kanser Hücrelerindeki IL-6’in Neden Olduğu İnflamatuar Tepkiyi Azaltır

Abstract

Interleukin-6 (IL-6) is a pro-inflammatory cytokine critical in immunoregulation. Aberrant IL-6 signaling has been implicated in various diseases including inflammation-associated cancer. Sirtuin-2 (SIRT2) is a cytoplasmic deacetylase and is generally considered a tumor suppressor. SIRT2 gene removed mouse develops tumors in many organs, primarily in the liver and breast tissues as the mouse ages. The purpose of the study was to investigate the roles of SIRT2 on IL-6 induced inflammatory response in mouse embryonic fibroblasts (MEFs) with SIRT2 gene removed and HeLa cervical cancer cell lines that overexpress SIRT2 gene. Immunoprecipitation and immunoblotting techniques were utilized in the study. SIRT2 interacts with JAK1, which is one of the downstream proteins of IL-6. We also found that overexpression of SIRT2 in HeLa cervical cancer cells decreases IL-6 induced inflammatory response by decreasing the activity of JAK1. These results suggest that SIRT2 has a protective role against chronic inflammatory diseases including inflammationassociated cancer.

SIRT2 mediated downregulation of FOXM1 in response to TGFβ through the RAF-MEK-ERK signaling pathway in colon cancer

“…Forty micrograms (µg) of each homogenate were loaded into each well and proteins were resolved by 10% tris-glycinesodium dodecyl sulfate-polyacrylamide gel electrophoresis (TG SDS-PAGE). Immunoblotting on polyvinylidene (PVDF) membranes was performed using the Trans-blot Turbo transfer system (BioRAD, CA, USA) as described [28,29]. Membranes were incubated with anti-FOXM1 (Santa Cruz Biotechnology, USA), anti-SIRT2 and anti-Flag antibody (Sigma, USA), anti-actin, anti-GAPDH, anti-tubulin and anti-P-ERK1/2 (all fom Cell Signaling, MA, USA) primary antibodies for 16 h at 4°C.…”