Abstract
N6-methyladenosine (m6A) is the most abundant internal RNA modification and plays a critical role in carcinogenesis and tumor progression. As a powerful m6A reader, YTHDF1 is implicated in multiple malignancies. However, the functions and underlying mechanisms of YTHDF1 in esophageal cancer (ESCA) are elusive. Here, we revealed that YTHDF1 expression was remarkably up-regulated in ESCA and linked with poor prognosis. Functionally, YTHDF1 promoted ESCA cell proliferation, migration, and metastasis in vitro and in vivo. Mechanistically, we demonstrated that TINAGL1 might be a potential target of YTHDF1. We revealed that YTHDF1 recognized and bound to m6A-modified sites of TINAGL1 mRNA, resulting in enhanced translation of TINAGL1. Furthermore, TINAGL1 knockdown partially rescued tumor-promoting effects of YTHDF1 overexpression. Therefore, we unveil that YTHDF1 facilitates ESCA progression by promoting TINAGL1 translation in an m6A-dependent manner, which offers an attractive therapeutic target for ESCA.