TOM1L1 mediated the sort of tumor suppressive miR-378a-3p into exosomes and the excretion out of cells to promote ESCC progression.

Abstract

Exosomes mediate cell-to-cell communication by releasing miRNAs, mRNA, etc. However, there is little research about the effects on the donor cells after miRNAs are excreted out of cells through exosomes. Here, we found that miR-378a-3p was specifically enriched in exosomes and inhibited cell proliferation, migration, invasion, and colony formation in ESCC. In addition, miR-378a-3p was sorted into exosomes through TOM1L1 and extracted mainly out of ESCC cells. Overexpression of TOM1L1 led to tumor suppressor miR-378a-3p accumulation in exosomes rather than in donor cells, promoting ESCC progression. Moreover, miR-378a-3p targets DYRK1A that directly binds to NPM1 and the phosphorylation state of NPM1 at Ser125 to suppress tumor growth. Taken together, our findings demonstrate that TOM1L1-mediated the tumor suppressor miR-378a-3p into exosomes and excreted out of cells to promote tumor progression.