p53-induced long non-coding RNA PGM5-AS1 inhibits the progression of esophageal squamous cell carcinoma through regulating miR-466/PTEN axis

Abstract

A growing body of evidence suggests that long non-coding RNA (lncRNA) is aberrantly expressed in human cancer and linked to cancer initiation and development. We previously identified Homo sapiens PGM5 antisense RNA 1 (PGM5-AS1) as a novel esophageal squamous cell carcinoma (ESCC)-related lncRNA by performing high-throughput RNA sequencing. However, its clinical implication and biological function in ESCC are still uncharacterized. In the present study, we found that PGM5-AS1 was frequently downregulated in ESCC tissues, plasma, and cell lines, and low PGM5-AS1 expression was positively correlated with poor differentiation, advanced tumor node metastasis (TNM) stage, and lymph node metastasis. Importantly, PGM5-AS1 was identified to be an effective diagnostic and prognostic biomarker for ESCC patients. Functional experiments revealed that exogenous expression of PGM5-AS1 significantly suppressed the proliferation, migration, and invasion of ESCC cells in vitro as well as tumor growth in vivo. Mechanistically, PGM5-AS1 was transcriptionally activated by p53 and it could directly interact with and sequester miR-466 to elevate PTEN expression, thereby inhibiting ESCC progression. Overall, our data indicate that PGM5-AS1 is a novel tumor suppressor in ESCC and restoration of PGM5-AS1 may be a promising avenue for treatment of ESCC patient.