Abstract
Esophageal squamous cell carcinoma (ESCC) is a leading lethal cancer in the digestive system. Tumor-associated macrophages (TAMs) are key participators in ESCC progression. Mounting evidence has testified the regulatory function of Synoviolin (SYVN1) in cancer development. However, the correlation between SYVN1 and TAM polarization remains unclear. As a result, the goal of the present study was to shed light on the new mechanism of SYVN1 in ESCC. It was found that SYVN1 was upregulated at mRNA and protein levels in tissue samples and cells of ESCC. Knockdown of SYVN1 attenuated the malignant behaviors of ESCC cells in vitro and in vivo. Of note, we verified that silencing SYVN1 contributed to the polarization of TAMs into M1 subtype. Moreover, our findings demonstrated that SYVN1 mediated cell pyroptosis through modulating TAM polarization. More than that, we explored the relationship between SYVN1 and pivotal modulatory factors of NF-κB signaling pathway. Our observations revealed that SYVN1 directly bound with DEAD-box helicase 5 (DDX5) and eukaryotic translation elongation factor 1 alpha 2 (eEF1A2) to enhance their expression. Besides, silencing of SYVN1 inhibited the activation of nuclear factor kappa B (NF-κB) pathway, and overexpression of DDX5 or eEF1A2 abolished the role of SYVN1 deficiency in NF-κB pathway. Overall, this study illustrated that SYVN1 induced ESCC progression by promoting the M2 polarization of TAMs and activating NF-κB pathway.