TAMs-derived exosomal Meg8 promotes the EMT and metastasis of SACC by regulating EGFR through sponge absorption of miR-148a-3p

Abstract Tumor-associated macrophages (TAMs) infiltrate extensively in salivary adenoid cystic carcinoma (SACC) tissues. Our previous study found that TAMs were significantly associated with the tumor metastasis and poor patients’ prognosis. However, the role and molecular mechanism of TAMs in SACC metastasis are still to be elucidated. Present study found that TAMs-derived exosomes can be internalized by SACC cells, initiating the epithelial-mesenchymal transition (EMT) process of SACC cells. TAMs-derived exosomal RNA sequencing and metastasis-related SACC tissues RNA sequencing suggested that Lnc-Meg8 was involved in TAMs-SACC interaction. RNA fluorescent in situ hybridization, RNA immunoprecipitation, and other in vitro assays revealed that TAMs-derived exosomes transferred Lnc-Meg8 to SACC cells, which promoted EGFR expression via sponge absorption of miR-148a-3p, thus promoting the EMT process of SACC cells. In vivo fluorescence imaging and immunohistochemical staining confirmed that inhibition of TAMs-derived exosomal Meg8 significantly improved the therapeutic efficacy of EGFR inhibitor cetuximab on the EMT and metastasis of SACC cells. In summary, our results demonstrated that the TAMs-derived exosomes promoted the EMT process of SACC cells via the Lnc-Meg8/miR-148a-3p/EGFR molecular axis. Blocking exosomal Lnc-Meg8 of TAMs may be a potential therapeutic strategy for SACC.