Long non-coding RNA-HAGLR suppressed tumor growth of lung adenocarcinoma through epigenetically silencing E2F1

Exp Cell Res. 2019 Sep 1;382(1):111461. doi: 10.1016/j.yexcr.2019.06.006. Epub 2019 Jun 10.


Emerging evidence indicates that long noncoding RNAs (LncRNAs) are new players in gene regulation but their mechanisms of action are mainly undocumented. In this study, we investigated LncRNA alterations that contribute to lung cancer by analyzing published microarray data in Gene Expression Obminus (GEO) and The Cancer Genome Atlas RNA (TCGA) sequencing data. Here, we reported that HAGLR (also called HOXD-AS1) was frequently down-regulated in lung adenocarcinoma (LUAD) tissues, and decreased HAGLR expression was clinically associated with shorter survival of LUAD patients. Preclinical studies using multiple LUAD cells and in vivo mouse model indicated that HAGLR could attenuate LUAD cell growth in vitro and in vivo. Mechanistically, HAGLR could physically interact with DNMT1, and recruit DNMT1 on E2F1 promoter to increase local DNA methylation. Overall, our study demonstrated that HAGLR promoted LUAD progression by recruiting DNMT1 to modulate the promoter methylation and expression of E2F1, which expanded potential therapeutic strategies for LUAD treatment.

Keywords: DNMT1; E2F1; HAGLR; Lung adenocarcinoma; Tumor growth.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA (Cytosine-5-)-Methyltransferase 1 / physiology
  • DNA Methylation
  • DNA, Neoplasm / genetics
  • E2F1 Transcription Factor / antagonists & inhibitors
  • E2F1 Transcription Factor / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Genes, Tumor Suppressor*
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Protein Interaction Mapping
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology


  • DNA, Neoplasm
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • RNA, Small Interfering
  • long non-coding RNA HOXD-AS1, human
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human