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

Feb 10, 2020Experimental cell research

FTO may increase growth and movement of esophageal cancer cells by raising MMP13 levels

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Abstract

FTO expression in esophageal squamous cell carcinoma (ESCC) tissues was stronger than in adjacent normal tissues.

High FTO expression is associated with a trend toward poor prognosis in ESCC patients.
Silencing FTO leads to decreased growth and migration of ESCC cells.
Overexpression of FTO promotes increased growth and migration in ESCC cells.
FTO is required for the tumorigenicity of ESCC cells in mouse models.
MMP13 expression is significantly influenced by FTO knockdown, indicating a regulatory relationship.

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FTO, a demethylase for N-methyladenosine (mA) 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. 6 6

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

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