FTO-Mediated lncRNA-FNDRR Axis Demethylation Promotes Cell Proliferation, Invasion, and Migration in Esophageal Squamous Cell Carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and has a significant impact on patient survival and quality of life. The role of N6-methyladenosine (m6A) modification in the regulation of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) has been reported in various diseases, including cancer. Although the clinical value of lncRNA-FNDRR in predicting ESCC prognosis is well-established, its molecular mechanism in ESCC remains incompletely understood. Therefore, in this study, we aimed to investigate the involvement of the m6A-lncRNA-FNDRR axis in ESCC progression. Results revealed that overexpression of lncRNA-FNDRR exerted inhibitory effects on ESCC cell proliferation, migration, and invasion. Interestingly, knockdown of the demethylase enzyme fat mass and obesity-associated protein (FTO) resulted in similar effects to those achieved by overexpressing lncRNA-FNDRR in ESCC cells. Moreover, we found that FTO had the ability to reverse the m6A modification of lncRNA-FNDRR. Importantly, simultaneous knockdown of FTO and overexpression of lncRNA-FNDRR promoted ESCC cell proliferation and metastasis, suggesting a synergistic effect between these two factors. These results provide valuable insights into the molecular mechanisms underlying ESCC and highlight the significance of m6A modifications in this context. Further investigations on m6A modifications in ESCC are warranted to deepen our understanding of this disease and explore potential therapeutic strategies.