Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer

Cell Death Dis. 2020 Feb 28;11(2):155. doi: 10.1038/s41419-020-2338-y.

Abstract

Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown. In this study, we observed that lncRNA LDLRAD4-AS1 was located in the nucleus of CRC cells and that lncRNA LDLRAD4-AS1 was upregulated in most CRC specimens and cell lines. Overexpression of lncRNA LDLRAD4-AS1 was correlated with poor prognosis in CRC patients. LncRNA LDLRAD4-AS1 upregulation enhanced the migration and invasion of CRC cells in vitro and facilitated CRC metastasis in vivo. Mechanistic investigations suggested that lncRNA LDLRAD4-AS1 could decrease the expression of LDLRAD4 by disrupting the stability of LDLRAD4 mRNA, resulting in epithelial-to-mesenchymal transition (EMT) through upregulating Snail, thereby promoting metastasis in CRC. Our results demonstrated a previously unrecognized LDLRAD4-AS1-LDLRAD4-Snail regulatory axis involved in epigenetic and posttranscriptional regulation that contributes to CRC progression and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics*

Substances

  • LDLRAD4 protein, human
  • Membrane Proteins
  • RNA, Long Noncoding