Long noncoding RNA AFAP1-AS1 predicts a poor prognosis and regulates non-small cell lung cancer cell proliferation by epigenetically repressing p21 expression

Mol Cancer. 2018 May 24;17(1):92. doi: 10.1186/s12943-018-0836-7.


Background: Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the role and molecular mechanism and global genes that were mediated by lncRNA AFAP1-AS1 in non-small cell lung cancer (NSCLC) remain largely unknown.

Methods: Expression of AFAP1-AS1 was analyzed in 92 NSCLC tissues and cell lines by Quantitative real time polymerase chain reaction (qRT-PCR). The effect of AFAP1-AS1 on proliferation was evaluated by function assays both in in vitro and in vivo. RNA-seq assays were performed after knockdown AFAP1-AS1. RNA immunoprecipitation (RIP) was performed to confirm the interaction between AFAP1-AS1 and EZH2. Chromatin immunoprecipitation (ChIP) was used to study the promoter region of p21.

Results: AFAP1-AS1 expression was increased in NSCLC tissues and was correlated with clinical outcomes of NSCLC. Further experiments revealed that inhibition of its expression in NSCLC cells resulted in diminished cell growth in vitro and in vivo. RNA-seq revealed that knockdown of AFAP1-AS1 could induce the expression of p21. Mechanistic investigations found that AFAP1-AS1 could interact with EZH2 and recruit EZH2 to the promoter regions of p21, thus epigenetically repressing p21 expression.

Conclusions: Together, these results suggest that lncRNA AFAP1-AS1 may serve as a candidate prognostic biomarker and target for new therapies in human NSCLC.

Keywords: AFAP1-AS1; Cell proliferation; EZH2; NSCLC; p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Down-Regulation
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA


  • AFAP1-AS1 long noncoding RNA, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Long Noncoding
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein