MicroRNA-506 inhibits gastric cancer proliferation and invasion by directly targeting Yap1

Tumour Biol. 2015 Sep;36(9):6823-31. doi: 10.1007/s13277-015-3364-8. Epub 2015 Apr 7.

Abstract

Increasing evidence indicates that microRNA (miR)-506 plays a vital role in tumorigenesis; however, the role of miR-506 in gastric cancer (GC) is unclear and needs further investigation. In the present study, we showed that the decrease in the expression of miR-506 is associated with tumor size, pathological tumor node metastasis (TNM) stage, and lymph node metastasis in 63 GC patient tumors. We found that patients with lower expression of miR-506 had a poor prognosis than that with the patients with high expression of miR-506. Notably, the ectopic expression of miR-506 was sufficient to inhibit cell proliferation, invasion, and epithelial-mesenchymal transition in the GC cells. Moreover, results from luciferase reporter assays identified miR-506 as a direct regulator of Yes-associated protein 1 (Yap1). Reintroduction of Yap1 rescues miR-506-induced effects on SGC-7901 cell proliferation and invasion. This function of miR-506/Yap1 axis is clinically significant, as the level of miR-506 is inversely correlated with Yap1 mRNA expression in matched tissues. Thus, our study demonstrates that miR-506 may act as a tumor suppressor in GC and that the miR-506/Yap1 axis may help us better understand the molecular mechanisms of GC progression.

Keywords: Gastric cancer; Invasion; Proliferation; Yap1; miR-506.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis*
  • Adaptor Proteins, Signal Transducing / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Phosphoproteins / biosynthesis*
  • Phosphoproteins / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Transcription Factors
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN506 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human