Circ847 upregulation via CAFs suppresses salivary adenoid cystic carcinoma progression through VIM-EMT

Abstract

Salivary adenoid cystic carcinoma (SACC) is prone to metastasis, which strongly affects its prognosis. Cancer-associated fibroblasts (CAFs) play important roles in SACC metastasis. The purpose of this study was to identify and explore the key regulatory mechanisms of the altered expression of circRNAs in SACC CAFs.

In this study, we found that circRNA-847 (circ847) expression was inhibited by pretreatment with SACC CAFs. Cell function experiments confirmed that the downregulation of circ847 promoted the proliferation and metastasis of SACC cells and that overexpression of circ847 induced the opposite effects. Mechanistically, circ847 can bind to vimentin and regulate its stability, thereby regulating epithelial–mesenchymal transition (EMT)-related signaling. Histological staining of SACC patient specimens also confirmed that the expression of circ847 was negatively correlated with SACC lymph node and lung metastasis. As a proof of concept, we successfully inhibited SACC progression and metastasis in sciatic nerve invasion models and lung metastasis models of SACC by treating the mice with nanoparticle-encapsulated circ847 plasmids to induce circ847 overexpression.

This study demonstrated that circ847 expression is inhibited by CAFs. Restoring the expression of circ847 can effectively inhibit the progression of SACC, providing new research ideas for the study of effective prevention and treatment strategies for SACC and the prediction of SACC distant metastasis risk and prognosis.