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

Shaobo Mo, Long Zhang, Weixing Dai, Lingyu Han, Renjie Wang, Wenqiang Xiang, Zhimin Wang, Qingguo Li, Jun Yu, Jihang Yuan, Sanjun Cai, Guoxiang Cai

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number155
JournalCell Death and Disease
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2020

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ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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