RETRACTED: LINC00184 silencing inhibits glycolysis and restores mitochondrial oxidative phosphorylation in esophageal cancer through demethylation of PTEN

Abstract

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 in vitro and in vivo , 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, invasion, colony formation, and glycolysis of EC cells and tumour growth, 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 modulated 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 regulatory 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.

LncRNA‐mediated posttranslational modifications and reprogramming of energy metabolism in cancer

“…Some lncRNAs, such as LOC572558, LINC00184, LINC00470 (also known as C18orf2) and AK023948, have been associated with AKT phosphorylation and energy metabolic reprogramming in diseases, especially in cancer. One study showed that LINC00184 modulated glycolysis and mitochondrial oxidative phosphorylation in oesophageal cancer cells through inducing AKT phosphorylation [78]. In addition, Liu et al [79] demonstrated that LINC00470 was a positive regulator of AKT activation in glioblastoma cells.…”

Involvement of Long Non-Coding RNAs in Glucose Metabolism in Cancer

“…Zhao et al [ 62 ] investigated the function of long intergenic non-protein coding RNA 184 ( LINC00184 ) on glycolysis and mitochondrial oxidative phosphorylation of esophageal cancer cells. They found that highly expressed LINC00184 increases esophageal cancer cell proliferation, migration, invasion and colony formation.…”

Long noncoding RNA SNHG6 promotes carcinogenesis by enhancing YBX1‐mediated translation of HIF1α in clear cell renal cell carcinoma

“…For example, linc00184 exerts its oncogenic role by promoting glycolysis and suppressing mitochondrial oxidative phosphorylation in esophageal cancer. 27 Zhang et al revealed that lncRNA-MIF inhibits aerobic glycolysis and tumorigenesis by suppressing c-Myc and miR-586. 28 We revealed that regulation of carbohydrate metabolic process and response to hypoxia were significantly activated in response to SNHG6 altered expression in ccRCC cells.…”