Long non-coding RNA LUCAT1 is associated with poor prognosis in human non-small lung cancer and regulates cell proliferation via epigenetically repressing p21 and p57 expression

Oncotarget. 2017 Apr 25;8(17):28297-28311. doi: 10.18632/oncotarget.16044.

Abstract

Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor-node-metastasis (TNM) stage and overall survival (OS). Further experiments showed that LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo. Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest. We further demonstrated that LUCAT1 was associated with polycomb repressor complexes (PRC2) and that this association was required for epigenetically repression of p21 and p57, thus contributing to the regulation of NSCLC cell cycle and proliferation. In summary, our results show that LUCAT1 could regulate tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.

Keywords: LUCAT1; LncRNAs; non-small cell lung cancer (NSCLC); p21; p57.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Computational Biology / methods
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Models, Biological
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • RNA Interference*
  • RNA, Long Noncoding / genetics*

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p57
  • RNA, Long Noncoding
  • long non-coding RNA LUCAT1, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein