miRNA-105 and -128 function as rheostats modulating MMP-2 activities by downregulation of TIMP-2 and upregulation of MT1-MMP
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  • 作者:Jin Hee Kim ; Li-Hua Li ; Hua Cai ; Vu H. Nguyen ; Jung-Joon Min…
  • 关键词:microRNA ; Metastasis ; Matrix metalloproteinase ; MMP ; 2 ; MT1 ; MMP ; TIMP ; 2 ; Protein kinase D
  • 刊名:Genes & Genomics
  • 出版年:2016
  • 出版时间:February 2016
  • 年:2016
  • 卷:38
  • 期:2
  • 页码:217-223
  • 全文大小:1,189 KB
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  • 作者单位:Jin Hee Kim (1)
    Li-Hua Li (2)
    Hua Cai (3)
    Vu H. Nguyen (4)
    Jung-Joon Min (4)
    Boo Ahn Shin (1)
    Seok-Yong Choi (3)
    Yang Seok Koh (5)

    1. Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea
    2. Department of Pathogen Biology, Hainan Medical University, Haikou, Hainan, People’s Republic of China
    3. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea
    4. Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
    5. Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea
  • 刊物主题:Microbial Genetics and Genomics; Plant Genetics & Genomics; Animal Genetics and Genomics; Human Genetics;
  • 出版者:Springer Netherlands
  • ISSN:2092-9293
文摘
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

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