Tumor suppressor miR-24 restrains gastric cancer progression by downregulating RegIV

Mol Cancer. 2014 May 28:13:127. doi: 10.1186/1476-4598-13-127.

Abstract

Background: microRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests miR-24 plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-24 in gastric cancer (GC).

Methods: The expression of miR-24 in GC tissues compared with matched non-tumor tissues and GC cells was detected by qRT-PCR. Synthetic short single or double stranded RNA oligonucleotides and lentiviral vectors were used to regulate miR-24 expression in GC cells to investigate its function in vitro and in vivo.

Results: miR-24 was significantly downregulated in GC tissues compared with matched non-tumor tissues and was associated with tumor differentiation. Ectopic expression of miR-24 in SGC-7901 GC cells suppressed cell proliferation, migration and invasion in vitro as well as tumorigenicity in vivo by inducing cell cycle arrest in G0/G1 phase and promoting cell apoptosis. Furthermore, we identified RegIV as a target of miR-24 and demonstrated that miR-24 regulated RegIV expression via binding its 3' untranslated region.

Conclusions: miR-24 functions as a novel tumor suppressor in GC and the anti-oncogenic activity may involve its inhibition of the target gene RegIV. These findings suggest the possibility for miR-24 as a therapeutic target in GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Animals
  • Apoptosis
  • Base Sequence
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Vectors
  • Humans
  • Lectins, C-Type / genetics*
  • Lectins, C-Type / metabolism
  • Lentivirus / genetics
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Molecular Sequence Data
  • Pancreatitis-Associated Proteins
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • Lectins, C-Type
  • MIRN24 microRNA, human
  • MicroRNAs
  • Pancreatitis-Associated Proteins
  • REG4 protein, human
  • RNA, Small Interfering