FTO promotes cell proliferation and migration in esophageal squamous cell carcinoma through up-regulation of MMP13

FTO, a demethylase for N6-methyladenosine (m6A) modification, has been implicated in multiple tumors. However, its roles in esophageal squamous cell carcinoma (ESCC) remain uncovered. This study aims to evaluate the clinical relevance and functional roles in this disease. Through immunohistochemistry, qRT-PCR and Western blot analyses, we found FTO expression in ESCC tissues was stronger than that in adjacent normal tissues, and the survival curves displayed high FTO expression had a trend toward poor prognosis. Functionally, silencing of FTO inhibited ESCC cell growth and migration in CCK8, EdU, colony formation and transwell assays and FTO overexpression showed the opposite results. Furthermore, FTO was also required for the tumorigenicity of ESCC cells in nude mice. The data from RNA-seq analysis revealed that MMP13 expression was significantly affected by FTO knockdown. qRT-PCR and Western blot assays confirmed that MMP13 was positively regulated by FTO in both mRNA and protein levels. Additionally, the functional link between FTO and MMP13 was explored by CCK8 and transwell chamber approaches. These findings suggest that FTO is up-regulated and plays oncogenic roles in ESCC. MMP13 may function as a downstream target of FTO.