P53-regulated lncRNA uc061hsf.1 inhibits cell proliferation and metastasis in human esophageal squamous cell cancer

IUBMB Life. 2020 Mar;72(3):401-412. doi: 10.1002/iub.2196. Epub 2019 Nov 19.

Abstract

The expression of long noncoding RNAs (lncRNAs) is closely associated with cancer development and progression, making these lncRNAs potentially novel therapeutic targets. In this study, we aimed to explore the potential function of lncRNA-uc061hsf.1 in esophageal squamous cell carcinoma (ESCC). The expression of lncRNA-uc061hsf.1 in ESCC tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, and metastasis were detected via CCK-8, flow cytometry, and Transwell assays. The interaction between p53 and lncRNA uc061hsf.1 was analyzed using luciferase reporter gene and qRT-PCR. Through this approach, we identified the novel lncRNA uc061hsf.1, which was expressed in low level in ESCC and was correlated with lymph node metastasis and poor differentiation in ESCC patients. Knockdown or overexpression of lncRNA uc061hsf.1 in ESCC cells promoted or inhibited cell proliferation and metastasis, respectively. Mechanistically, lncRNA uc061hsf.1 was induced by p53, and luciferase reporter gene confirmed that lncRNA uc061hsf.1 was a direct transcriptional target of p53. We further found that uc061hsf.1 was able to regulate expression of the transcription factor FoxA1, thereby potentially influencing tumor cell migration. In conclusion, these results suggest that p53-regulated lncRNA uc061hsf.1 is a cancer suppressor gene which is associated with tumor progression in ESCC.

Keywords: FoxA1; esophageal squamous cell carcinoma; lncRNA uc061hsf.1; metastasis; p53; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 3-alpha / genetics
  • Humans
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53