The NR3C2-SIRT1 signaling axis promotes autophagy and inhibits epithelial mesenchymal transition in colorectal cancer

Colorectal Cancer (CRC) is one of the most aggressive and lethal cancers with a complex pathogenesis, there is an urgent need to find new drug therapeutic targets. This study highlights the important role of the NR3C2-SIRT1 signaling axis in the metastasis mechanism of CRC. Our findings revealed that the expression of NR3C2 in CRC tissues was lower than that in adjacent non-cancerous tissues, and was negatively correlated with N stage by bioanalysis, IHC, western blot and qRT-PCR. NR3C2 overexpression / knockdown can significantly inhibit / promote the migration and invasion of CRC cells, at the same time inhibit / promote EMT. Mechanically, the regulatory molecule SIRT1 was identified by RNA-seq, bioinformatics analysis, western blot and ChIP. SIRT1 was also involved in the metastasis process of CRC, and NR3C2 was found to regulate the expression of LC3B and SQSTM1/p62 in a SIRT1-dependent manner. Therefore, NR3C2 forms a signaling axis with SIRT1, which can directly promote Autophagy and inhibit EMT process in vivo and in vitro. Collectively, our findings suggest that NR3C2 - SIRT1 signal axis promote Autophagy and inhibit EMT, ultimately inhibits lung metastasis of CRC.