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

IUBMB Life. 2019 Oct;71(10):1492-1502. doi: 10.1002/iub.2069. Epub 2019 Jun 11.


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.

Keywords: PGM5-AS1; biomarker; esophageal squamous cell carcinoma; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • RNA, Long Noncoding / genetics*
  • Tumor Suppressor Protein p53 / genetics*


  • Biomarkers, Tumor
  • MIRN466 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • PTEN Phosphohydrolase
  • PTEN protein, human