Reciprocal control of lncRNA-BCAT1 and β-catenin pathway reveals lncRNA-BCAT1 long non-coding RNA acts as a tumor suppressor in colorectal cancer

Oncotarget. 2017 Apr 4;8(14):23628-23637. doi: 10.18632/oncotarget.15466.

Abstract

β-catenin plays a major role in tumor development and progression. The present study found that β-catenin was upregulated in 30 samples of colorectal cancer (CRC) tissue as compared to adjacent non-tumor tissues. Analysis of long non-coding RNA (lncRNA) expression profiles using the GSE18560 and GSE44097 datasets, which were generated via the Affymetrix plus 2.0 microarray platform and downloaded from the GEO database, revealed 20 differentially expressed lncRNAs following β-catenin knockdown. We focused on AK091631, a novel lncRNA, which we named lncRNA-β-catenin associated transcript 1 (LncRNA-BCAT1). lncRNA-BCAT1 expression was decreased in CRC tissues, and was negatively associated with β-catenin in both CRC tissues and cell lines. lncRNA-BCAT1 overexpression suppressed CRC cell growth and invasion by downregulating cyclin D1, c-Myc, and MMP-2. These results suggest that lncRNA-BCAT1 overexpression inhibits CRC cell growth and invasion via Wnt/β-catenin pathway blockade, and that lncRNA-BCAT1 is repressed by Wnt/β-catenin signaling. This evidence suggests that lncRNA-BCAT1 is a tumor suppressor and that lncRNA-BCAT1 may be an effective prognostic biomarker in CRC.

Keywords: colorectal cancer; lncRNA-BCAT1; long non-coding RNA; tumor suppressor; β-catenin.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • RNA, Long Noncoding / genetics*
  • Tumor Cells, Cultured
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / genetics*

Substances

  • CTNNB1 protein, human
  • RNA, Long Noncoding
  • beta Catenin
  • long non-coding RNA BCAT1, human