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Digestive Diseases and Sciences

, Volume 59, Issue 3, pp 598–606 | Cite as

PAX6, a Novel Target of microRNA-7, Promotes Cellular Proliferation and Invasion in Human Colorectal Cancer Cells

  • Yanwen Li
  • Yuehui Li
  • Yanhong Liu
  • Pingli Xie
  • Feng Li
  • Guancheng LiEmail author
Original Article

Abstract

Background

Paired box 6 (PAX6), a highly conserved transcriptional factor, has been implicated in tumorigenesis.

Aim

We aimed to explore the roles and molecular mechanisms of PAX6 and microRNA (miR-7) in colorectal cancer cells.

Methods

Tissue microarray immunohistochemistry and Western blot were applied to examine the PAX6 expression. Real-time RT-PCR and Western blot were performed to determine the expression of miR-7 and PAX6. Luciferase reporter assay was used to determine whether PAX6 was a target of miR-7. Effects of miR-7 and PAX6 on colorectal cell proliferation, cell cycle progression, colony formation and invasion were then investigated. Western blot was used to determine the activities of the ERK and PI3K signal pathways, as well as the protein expression of MMP2 and MMP9.

Results

The protein levels of PAX6 were gradually increased, while the expression of miR-7 was gradually reduced with malignancy of colorectal cancer. PAX6 was further identified as a target of miR-7, and its protein expression was negatively regulated by miR-7 in human colorectal cancer cells. Overexpression of PAX6 in Caco-2 and SW480 cells enhanced cellular proliferation, cell cycle progression, colony formation, and invasion, while miR-7 upregulation repressed these biological processes. Furthermore, the activities of ERK and PI3K signal pathways, as well as the protein levels of MMP2 and MMP9, were upregulated in PAX6-overexpressed Caco-2 and SW480 cells but deregulated in miR-7-overexpressed Caco-2 and SW480 cells.

Conclusions

Our study suggests that as a novel target of miR-7, PAX6 may serve as a promising therapeutic target for colorectal cancer.

Keywords

Colorectal cancer Paired box 6 (PAX6) MicroRNA-7 Proliferation Invasion 

Notes

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yanwen Li
    • 1
    • 2
  • Yuehui Li
    • 1
  • Yanhong Liu
    • 1
  • Pingli Xie
    • 1
  • Feng Li
    • 1
  • Guancheng Li
    • 1
    Email author
  1. 1.Tumor Immunobiology Laboratory of Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Ministry of HealthCentral South UniversityChangshaChina
  2. 2.Clinical LaboratoryThe First Affiliated Hospital of Nanhua UniversityHengyangChina

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