The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma

Cancer Lett. 2018 Mar 28;417:47-57. doi: 10.1016/j.canlet.2017.12.016. Epub 2017 Dec 14.

Abstract

Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.

Keywords: DNA methylation; DNA methyltransferase 1; Epigenetics; Esophagus squamous cell carcinoma; LUCAT1; Long-noncoding RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinogenesis / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics*
  • DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
  • DNA Methylation / genetics
  • Enzyme Stability
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Ubiquitination

Substances

  • RNA, Long Noncoding
  • long non-coding RNA LUCAT1, human
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human