Long noncoding RNA LINC01088 inhibits esophageal squamous cell carcinoma progression by targeting the NPM1-HDM2-p53 axis

Abstract

Esophageal squamous cell carcinoma (ESCC) is characterized by extensive metastasis and poor prognosis. Long noncoding RNAs (lncRNAs) have been shown to play important roles in ESCC. However, the specific roles of lncRNAs in ESCC tumorigenesis and metastasis remain largely unknown. Here, we investigate LINC01088 in ESCC. Differentially expressed LINC01088 levels are screened from the GEO database. We find that LINC01088 is expressed at low level in collected clinical samples and is correlated with vascular tumor emboli and poor overall survival time of patients after surgery. LINC01088 inhibits not only ESCC cell migration and invasion in vitro, but also tumorigenesis and metastasis in vivo. Mechanistically, LINC01088 directly interacts with nucleophosmin (NPM1) and increases the expression of NPM1 in the nucleoplasm compared to that in the nucleolar region. LINC01088 decreases mutant p53 (mut-p53) expression and rescues the transcriptional activity of p53 by targeting the NPM1-HDM2-p53 axis. LINC01088 may also interfere with the DNA repair function of NPM1 by affecting its translocation. Our results highlight the potential of LINC01088 as a prognostic biomarker and therapeutic target of ESCC.

Keywords

• esophageal squamous cell carcinoma
• LINC01088
• nucleophosmin
• p53