Inhibition of microRNA-17/20a suppresses cell proliferation in gastric cancer by modulating UBE2C expression

Oncol Rep. 2015 May;33(5):2529-36. doi: 10.3892/or.2015.3835. Epub 2015 Mar 5.

Abstract

microRNAs (miRNAs) are small non-coding RNAs that potentially play a critical role in carcinogenesis. Increasing evidence indicates that the miR-17/20 cluster is upregulated in numerous types of human cancers including gastric cancer which suggests that the miR-17/20 cluster may play an important role in tumorigenesis. However, its role in gastric cancer carcinogenesis remains poorly defined due to the lack of target gene information. The aim of the present study was to investigate the target genes of the miR-17/20 cluster and their role in the tumor growth of gastric cancer. We found that both miR-17 and miR-20a (miR-17/20a) target the UBE2C gene in gastric cancer cells. Luciferase assay, qRT-PCR and western blot analysis confirmed that UBE2C is a direct target of miR‑17/20a in gastric cancer cells. Our results showed that the expression of UBE2C was positively regulated by miR-17/20a at both the mRNA and protein levels. Moreover, miR-17/20a was upregulated and positively associated with UBE2C in the gastric cancer tissues when compared to the adjacent nontumor tissues. Inhibition of miR-17/20a in gastric cancer cells was statistically correlated with a decrease in cell growth. These results demonstrate that upregulation of miR-17/20a promotes gastric cancer cell growth by targeting UBE2C and inhibition of their levels is a potentially promising therapeutic strategy for gastric cancer.

MeSH terms

  • Carcinogenesis / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Up-Regulation / genetics

Substances

  • MIRN20a microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • UBE2C protein, human
  • Ubiquitin-Conjugating Enzymes