An oncogenic role of miR-592 in tumorigenesis of human colorectal cancer by targeting Forkhead Box O3A (FoxO3A)

Expert Opin Ther Targets. 2016 Jul;20(7):771-82. doi: 10.1080/14728222.2016.1181753. Epub 2016 May 11.

Abstract

Objective: A microRNA (miRNA) that functionally downregulates the expression of tumor suppressors can be defined as an oncomir. Here, we interrogate the biological significance of miR-592 in colorectal cancer (CRC).

Research design and methods: The expression of miR-592 in CRC tissues and cell lines was ascertained by qRT-PCR assay, and the expression of its target gene was determined by immunohistochemistry staining. The oncogenic role of miR-592 was assessed in terms of cell proliferation, migration, and clonogenicity in vitro, whereas the tumorigenicity was assessed by inhibiting endogenous miR-592 in CRC cells in vivo.

Results: A striking upregulation of miR-592 was observed in CRC tissues and cell lines compared to the matched adjacent non-tumor tissues and normal colon cells. Importantly, Forkhead Box O3A (FoxO3A) was identified as a novel target of miR-592. miR-592 inhibitor exhibited a significant reduction of migration, proliferation, and clonogenicity in CRC cells. These cells also displayed a decreased tumorigenicity in SCID mice relative to the control cells.

Conclusion: These data suggest that miR-592 may promote the progression and metastasis, in part, by targeting FoxO3A in CRC. miR-592 may be a novel target for CRC treatment and antagomir-592 may inhibit the proliferation and metastasis of CRC cells.

Keywords: Antagomir; Forkhead Box O3A; colorectal cancer; miR-592; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Down-Regulation
  • Female
  • Forkhead Box Protein O3 / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • MicroRNAs / genetics*
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN592 microRNA, human
  • MicroRNAs