AL355338 acts as an oncogenic lncRNA by interacting with protein ENO1 to regulate EGFR/AKT pathway in NSCLC

Non-small cell lung cancer (NSCLC) is a malignancy with considerable morbidity and mortality. Abnormal metabolism is a hallmark of cancer; however, the mechanism of glycolysis regulation in NSCLC progression is not completely understood. Recent studies suggest that some dysregulated long non-coding RNAs (lncRNAs) play important roles in tumor metabolic reprogramming.

This study indicates that AL355338 confers an aggressive phenotype to NSCLC, and targeting it might be an effective therapeutic strategy.

To identify glycolysis-associated-lncRNAs in NSCLC, we compared RNA-sequencing

AL355338 was an upregulated glycolysis-associated lncRNA in NSCLC. Functional assays revealed that AL355338 was critical for promoting aerobic glycolysis and NSCLC progression. Mechanistic investigations showed that AL355338 directly bound with alpha-enolase (ENO1) and enhanced the protein's stability by modulating its degradation and ubiquitination. A positive correlation was observed between AL355338 and ENO1 in NSCLC, and ENO1 was subsequently confirmed to be responsible for the oncogenic role of AL355338. Furthermore, AL355338 was capable of modulating ENO1/EGFR complex interaction and further activating EGFR-AKT signaling. Conclusions: This study indicates that AL355338 confers an aggressive phenotype to NSCLC, and targeting it might be an effective therapeutic strategy.