Tumor suppressor microRNA-18a regulates tumor proliferation and invasion by targeting TBPL1 in colorectal cancer cells

Mol Med Rep. 2015 Nov;12(5):7643-8. doi: 10.3892/mmr.2015.4335. Epub 2015 Sep 17.

Abstract

Recent advances in the understanding of microRNA have rendered microRNAs (miRNAs) a compelling novel class of biomarker in cancer biology. However, the specific function of miRNA‑18a (miR‑18a) in colorectal cancer (CRC) remains unclear. In the present study, the role of miR‑18a in the carcinogenesis of CRC was investigated. miR‑18a expression was assessed in CRC specimens and cell lines using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The targets of miR‑18a were predicted using bioinformatics tools. Luciferase reporter assays were used to confirm the functional association between miR‑18a and its target genes. The effect of miR‑18a on cell proliferation, invasion and migration was confirmed in vitro by a methylthiazol tetrazolium assay, cell invasion assay, and wound healing assay. Gene and protein expression was examined using RT‑qPCR and western blotting, respectively. It was demonstrated that the expression of miR‑18a in CRC tissues and cell lines was markedly lower than in normal control tissues and cells, respectively. In addition, miR‑18a inhibited cell proliferation, invasion and migration in CRC cells. Moreover, TATA box‑binding protein‑like protein 1 (TBPL1) was identified as a potential target gene of miR‑18a in the bioinformatics analysis and luciferase reporter assays, and miR‑18a directly inhibited TBPL1 expression by targeting its 3'‑untranslated region. Furthermore, TBPL1 was downregulated and inversely correlated with miR‑18a expression in tissues. These findings demonstrate that miR‑18a exhibits a protective role in CRC via inhibiting proliferation, invasion and migration of CRC cells by directly targeting the TBPL1 gene.

MeSH terms

  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colon / metabolism
  • Colon / pathology*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Rectum / metabolism
  • Rectum / pathology*
  • TATA Box Binding Protein-Like Proteins / genetics*

Substances

  • MIRN18A microRNA, human
  • MicroRNAs
  • TATA Box Binding Protein-Like Proteins
  • TBPL1 protein, human