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miR-181a-5p Inhibits Cancer Cell Migration and Angiogenesis via Downregulation of Matrix Metalloproteinase-14

Yiyi Li1, Cem Kuscu2, Anna Banach2

  • 1Department of Medicine/Cancer Prevention, Stony Brook University, Stony Brook, New York. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Cancer Research
|May 16, 2015
PubMed

Insights

MicroRNA miR-181a-5p downregulation elevates matrix metalloproteinase MMP-14 (MT1-MMP) in aggressive cancers. Restoring miR-181a-5p levels inhibits cancer cell invasion and metastasis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Matrix metalloproteinase MMP-14 (MT1-MMP) upregulation correlates with poor cancer prognosis.
  • Mechanisms driving MMP-14 elevation in tumors remain largely unknown.

Purpose of the Study:

  • To investigate the role of miR-181a-5p in regulating MMP-14 expression in aggressive breast and colon cancers.
  • To elucidate the functional consequences of the miR-181a-5p/MMP-14 axis on cancer progression and metastasis.

Main Methods:

  • Analysis of miR-181a-5p and MMP-14 expression in clinical cancer specimens.
  • Bioinformatics prediction and reporter gene assays to validate miR-181a-5p binding to MMP-14.
  • In vitro experiments assessing the impact of miR-181a-5p modulation on cancer cell behavior.
  • In vivo chick chorioallantoic membrane assays to evaluate invasion and angiogenesis.

Main Results:

  • miR-181a-5p was inversely correlated with MMP-14 expression in aggressive breast and colon cancers.
  • MMP-14 was upregulated, and miR-181a-5p downregulated at the invasive front of tumors.
  • miR-181a-5p directly targets the 3'-untranslated region of MMP-14, reducing its expression.
  • Modulating miR-181a-5p levels significantly affected cancer cell migration, invasion, pro-MMP-2 activation, angiogenesis, and in vivo invasion.

Conclusions:

  • miR-181a-5p posttranscriptionally regulates MMP-14 expression in cancer.
  • The miR-181a-5p/MMP-14 pathway is a critical determinant of cancer cell invasion and metastasis.
  • Elevating miR-181a-5p represents a potential therapeutic strategy to inhibit cancer metastasis.

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