DNMT3A-mediated down-regulation of microRNA-105 promotes gastric cancer cell proliferation

Eur Rev Med Pharmacol Sci. 2017 Aug;21(15):3377-3383.

Abstract

Objective: It has been well-established that microRNAs (miRNAs), a class of short non-coding RNA molecules, play an important role in the development of gastric cancer. In the present study, we focused on miR-105, a novel miRNA not previously linked to gastric cancer.

Patients and methods: 36 paired surgically resected gastric cancer tissues and matched adjacent normal tissues were used to detect the expression of miR-105. AGS cells were used to overexpress or silence of miR-105 and to determine its effect on several tumorigenic properties. A cell proliferation enzyme-linked immunosorbent assay was used to analyze the incorporation of BrdU during DNA synthesis of AGS cells. Total cDNA from AGS cells was used to amplify the 3'-UTR of YY1 by PCR and luciferase activity was determined using the Dual-Luciferase Reporter Assay System RESULTS: We found that expression of miR-105 was reduced in gastric cancer tissues, compared with adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-105 suppressed, whereas its inhibition promoted cell viability and proliferation. We further identified Yin Yang 1 (YY1) as a direct target of miR-105, by which miR-105 exerted its anti-proliferative role. Moreover, we found that DNMT3A was responsible for the down-regulation of miR-105 in gastric cancer cells.

Conclusions: Our data demonstrate that miR-105 inhibits gastric cancer cell proliferation and progression, which might provide a therapeutical target for cancer therapy.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methyltransferase 3A
  • Down-Regulation / genetics
  • Gene Silencing
  • Genes, p53 / genetics
  • Humans
  • MicroRNAs / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • YY1 Transcription Factor / biosynthesis
  • YY1 Transcription Factor / genetics

Substances

  • 3' Untranslated Regions
  • DNMT3A protein, human
  • MIRN105 microRNA, human
  • MicroRNAs
  • YY1 Transcription Factor
  • YY1 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A