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Genes & Genomics

, Volume 38, Issue 2, pp 217–223 | Cite as

miRNA-105 and -128 function as rheostats modulating MMP-2 activities by downregulation of TIMP-2 and upregulation of MT1-MMP

  • Jin Hee Kim
  • Li-Hua Li
  • Hua Cai
  • Vu H. Nguyen
  • Jung-Joon Min
  • Boo Ahn ShinEmail author
  • Seok-Yong ChoiEmail author
  • Yang Seok KohEmail author
Research Article

Abstract

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that remodel and degrade the extracellular matrix. Of various MMPs, MMP-2 plays an important role in tumor metastasis. Recently, microRNAs with pro- or anti-metastatic effects were collectively referred to as metastamiRs. We screened 215 human miRNA mimics for modulators of MMP-2 activities in HT-1080 cells, and found that miR-105 and miR-128 promote MMP-2 activities. Bioinformatics analysis predicted that miR-105 and miR-128 both bind to the 3′ untranslated region (UTR) of TIMP-2, an inhibitor of MMP-2 activities. This prediction was verified by reduced luciferase activity in HT-1080 cells co-transfected with miR-105 or miR-128 mimics and plasmids encoding luciferase fused to 3′ UTR of TIMP2. In addition, Western blotting showed that transfection of HT-1080 cells with miR-105 or miR-128 suppressed TIMP-2 levels and enhanced levels of MT1-MMP, an activator of MMP-2 activities. The mechanism by which miR-128 upregulates MT1-MMP was determined to be downregulation of PRKD1, an inhibitor of MT1-MMP, at least in part. Cell invasion assays using Matrigel demonstrated that HT-1080 cells transfected with miR-105 or miR-128 are more invasive as compared to control cells. Taken together, these findings show that miR-105 and miR-128 are metastamir promoting MMP-2 activities via simultaneously downregulating TIMP-2 and upregulating MT1-MMP, and may provide a platform for the development of therapeutics against metastasis.

Keywords

microRNA Metastasis Matrix metalloproteinase MMP-2 MT1-MMP TIMP-2 Protein kinase D 

Notes

Acknowledgments

This work was supported by Chonnam National University Hospital Biomedical Research Institute (CRI 11002-1 and HCRI 14023-1) and Chonnam National University (2011-2495). We thank Gary Jenkins for English editing and Eun Young Choi for encouragement.

Compliance with ethical standards

Conflict of interest

The authors have declared that they have no conflicts of interests.

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Copyright information

© The Genetics Society of Korea and Springer-Science and Media 2015

Authors and Affiliations

  1. 1.Department of MicrobiologyChonnam National University Medical SchoolGwangjuRepublic of Korea
  2. 2.Department of Pathogen BiologyHainan Medical UniversityHaikouPeople’s Republic of China
  3. 3.Department of Biomedical SciencesChonnam National University Medical SchoolGwangjuRepublic of Korea
  4. 4.Department of Nuclear MedicineChonnam National University Medical SchoolGwangjuRepublic of Korea
  5. 5.Department of SurgeryChonnam National University Medical SchoolGwangjuRepublic of Korea

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