MicroRNA-155 expression inversely correlates with pathologic stage of gastric cancer and it inhibits gastric cancer cell growth by targeting cyclin D1

J Cancer Res Clin Oncol. 2016 Jun;142(6):1201-12. doi: 10.1007/s00432-016-2139-y. Epub 2016 Mar 8.

Abstract

Purpose: MicroRNAs (miRs) have been frequently reported dysregulating in tumors and playing a crucial role in tumor development and progression. However, the expression of miR-155 and its role in gastric cancer (GC) are still obscure.

Methods: qRT-PCR was applied to detect miR-155 expression in 60 matched GC samples and four GC cell lines, and the relationship between miR-155 levels and clinicopathological features of GC was analyzed. Next, the effects of miR-155 on GC cell growth were evaluated by gain- and loss-of-function analysis. Finally, the target gene(s) of miR-155 in GC cells were explored.

Results: Our results revealed that miR-155 levels were significantly lower in both GC tissues and GC cell lines than in their normal controls, and its expression inversely correlated with tumor size and the pathologic stage. Moreover, our study showed that enforced expression of miR-155 impaired GC cell proliferation, promoted G1 phase arrest and induced apoptosis in vitro. In addition, we identified cyclin D1 as the direct target of miR-155, and knockdown of cyclin D1 partially phenocopied the role of miR-155 in GC cells.

Conclusions: Our findings suggest that miR-155 may act as a potential diagnostic marker for early-stage GC and may represent a novel therapeutic target for GC treatment.

Keywords: Apoptosis; Cell cycle; Cyclin D1; Gastric cancer; MicroRNA-155; Proliferation.

MeSH terms

  • Apoptosis
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cyclin D1 / genetics*
  • Down-Regulation
  • Humans
  • MicroRNAs / genetics*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • MIRN155 microRNA, human
  • MicroRNAs
  • Cyclin D1