Fusobacterium nucleatum induced exosomal HOTTIP promotes gastric cancer progression through miR-885-3p/EphB2 axis.

Abstract

Recent studies have demonstrated that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory non-coding RNAs and are crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. And, HOTTIP was upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging miR-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression via the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.