LINC00184 Silencing Inhibits Glycolysis and Restores Mitochondrial Oxidative Phosphorylation in Esophageal Cancer Through Demethylation of PTEN

Background: Total lesion glycolysis has been reported to be a satisfactory predictor of survival in patients with locally advanced esophageal cancer (EC). The aim of the present study is to investigate the function of long intergenic non-protein coding RNA 184 (LINC00184) on the EC cell glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). Methods: The expression of LINC00184 was determined to be highly expressed and PTEN was poorly expressed in EC tissues and cells by RT-qPCR. In order to evaluate the effects of LINC00184 on cellular process, gain- and loss-of-function approaches were performed to alter the expression of LINC00184 and PTEN in EC cells. Results: Silencing of LINC00184 was observed to inhibit the proliferation, migration and glycolysis of ECs, while the mitochondrial OXPHOS was restored. By recruiting DNMT1, LINC00184 enhanced the promoter methylation of PTEN. Inhibition of PTEN promoter methylation suppressed EC glycolysis, whereas, improved mitochondrial OXPHOS. Mechanically, LINC00184 modulate glycolysis and mitochondrial OXPHOS in EC cells through induction of the Akt phosphorylation. After blockage of Akt signaling pathway by an Akt inhibitor, LY294002, the regulator effects of LINC00184 on the glycolysis and mitochondrial OXPHOS of EC cells were reversed. Conclusion: Taken together, the LINC00184/PTEN/Akt axis mediates glycolysis and mitochondrial OXPHOS in EC cells. This study highlighted a potential intervention target for treating EC. Funding Statement: The authors state: "none." Declaration of Interests: The authors declare: "none." Ethics Approval Statement: Written consents were obtained from all patients prior to surgery and the study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University. All experiments involving human tissue were performed according to the principles of the “Helsinki declaration.”