MiR-143 inhibits cell proliferation and invasion by targeting DNMT3A in gastric cancer

Tumour Biol. 2017 Jul;39(7):1010428317711312. doi: 10.1177/1010428317711312.

Abstract

Increasing evidence has suggested that MircroRNAs (miRNAs) dysregulated in pathogenesis and tumorigenicity in human cancers including gastric cancer (GC). MiR-143 had been reported to function as tumor suppressor in GC progression, however, the underlying function of miR-143 in GC still need to be well known. In the study, we revealed that miR-143 was significantly down-regulated in GC cell lines. Upregulation of miR-143 inhibited cell proliferation, invasion, S phase cell proportion and cell cycle related protein levels of Cyclin D1, CDK4 and CDK6 in GC. Furthermore, luciferase reporter assays demonstrated that DNMT3A was a direct target of miR-143 and Upregulation of miR-143 inhibited the DNMT3A mRNA and protein expression levels in GC cells. Moreover, we demonstrated that DNMT3A knockdown rescued the promoting effect of miR-143 inhibitor on cell proliferation in GC. Thus, these results demonstrated that miR-143 targeted DNMT3A in GC cells and inhibit GC tumorigenesis and progression, which may provide a novel therapeutic target of GC.

Keywords: DNMT3A; Gastric cancer; cell invasion; cell proliferation; miR-143.

MeSH terms

  • Carcinogenesis / genetics*
  • Cell Cycle / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 6 / genetics
  • DNA (Cytosine-5-)-Methyltransferases / biosynthesis*
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methyltransferase 3A
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • CCND1 protein, human
  • DNMT3A protein, human
  • MIRN143 microRNA, human
  • MicroRNAs
  • Cyclin D1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6