miR-664a-3p functions as an oncogene by targeting Hippo pathway in the development of gastric cancer

Cell Prolif. 2019 May;52(3):e12567. doi: 10.1111/cpr.12567. Epub 2019 Mar 18.

Abstract

Objectives: It has been accounted that miR-664a-3p has different functions in several malignancies; however, the precise role and underlying mechanism in gastric cancer have not been elucidated. Our study aims to explore the function of miR-664a-3p on the progression of gastric cancer (GC).

Methods: qRT-PCR was applied to detect the expression of miR-664a-3p in GC tissues and cells. The functions of miR-664a-3p on GC in vitro were examined by cell proliferation assay, and transwell assay. Related proteins of epithelial-mesenchymal transition (EMT) and signal pathway were evaluated by Western blot and immunofluorescence analysis. The bioinformatic, dual-luciferase assay or ChIP assay were employed to identify the interaction between miR-664a-3p and its target gene or Foxp3. The effects in vivo were investigated through a mouse tumorigenicity model.

Results: miR-664a-3p was frequently upregulated in GC tissues and cells. Elevated expression of miR-664a-3p significantly promoted proliferation and invasion in vitro and in vivo. MOB1A was confirmed to be a target of miR-664a-3p and restoration of MOB1A attenuated the effects of miR-664a-3p. A series of investigations indicated that miR-664a-3p contributed to EMT process and inactivated the Hippo pathway by downregulating MOB1A.

Conclusion: Taken together, we revealed that miR-664a-3p functions as an oncogene by targeting Hippo pathway in the development of gastric cancer.

Keywords: GC; Hippo; MOB1A; metastasis; miR-664a-3p; proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Heterografts
  • Hippo Signaling Pathway
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Oncogenes*
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN664 microRNA, human
  • MOB1A protein, human
  • MicroRNAs
  • Protein Serine-Threonine Kinases