miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14

Yiyi Li, Cem Kuscu, Anna Banach, Qian Zhang, Ashleigh Pulkoski-Gross, Deborah Kim, Jingxuan Liu, Eric Roth, Ellen Li, Kenneth R. Shroyer, Paula I. Denoya, Xiaoxia Zhu, Longhua Chen, Jian Cao

Research output: Contribution to journalArticle

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Abstract

Upregulation of matrix metalloproteinase MMP-14 (MT1-MMP) is associated with poor prognosis in cancer patients, but it is unclear how MMP-14 becomes elevated in tumors. Here, we show that miR-181a-5p is downregulated in aggressive human breast and colon cancers where its levels correlate inversely with MMP-14 expression. In clinical specimens, enhanced expression of MMP-14 was observed in cancer cells located at the invasive front of tumors where miR-181a-5p was downregulated relative to adjacent normal cells. Bioinformatics analyses defined a potential miR-181a-5p response element within the 3′-untranslated region of MMP-14 that was validated in reporter gene experiments. Ectopic miR-181a-5p reduced MMP-14 expression, whereas miR-181a-5p attenuation elevated MMP-14 expression. In support of a critical relationship between these two genes, miR-181a-5p-mediated reduction of MMP-14 levels was sufficient to decrease cancer cell migration, invasion, and activation of pro-MMP-2. Furthermore, this reduction in MMP-14 levels was sufficient to reduce in vivo invasion and angiogenesis in chick chorioallantoic membrane assays. Taken together, our results establish the regulation of MMP-14 in cancers by miR-181a-5p through a posttranscriptional mechanism, and they further suggest strategies to elevate miR-181a-5p to prevent cancer metastasis.

Original languageEnglish (US)
Pages (from-to)2674-2685
Number of pages12
JournalCancer Research
Volume75
Issue number13
DOIs
StatePublished - Jul 1 2015

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Matrix Metalloproteinase 14
Matrix Metalloproteinases
Cell Movement
Down-Regulation
Neoplasms
Chorioallantoic Membrane
Response Elements
3' Untranslated Regions
Computational Biology
Reporter Genes
Colonic Neoplasms
Up-Regulation
Breast Neoplasms
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14. / Li, Yiyi; Kuscu, Cem; Banach, Anna; Zhang, Qian; Pulkoski-Gross, Ashleigh; Kim, Deborah; Liu, Jingxuan; Roth, Eric; Li, Ellen; Shroyer, Kenneth R.; Denoya, Paula I.; Zhu, Xiaoxia; Chen, Longhua; Cao, Jian.

In: Cancer Research, Vol. 75, No. 13, 01.07.2015, p. 2674-2685.

Research output: Contribution to journalArticle

Li, Y, Kuscu, C, Banach, A, Zhang, Q, Pulkoski-Gross, A, Kim, D, Liu, J, Roth, E, Li, E, Shroyer, KR, Denoya, PI, Zhu, X, Chen, L & Cao, J 2015, 'miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14', Cancer Research, vol. 75, no. 13, pp. 2674-2685. https://doi.org/10.1158/0008-5472.CAN-14-2875
Li, Yiyi ; Kuscu, Cem ; Banach, Anna ; Zhang, Qian ; Pulkoski-Gross, Ashleigh ; Kim, Deborah ; Liu, Jingxuan ; Roth, Eric ; Li, Ellen ; Shroyer, Kenneth R. ; Denoya, Paula I. ; Zhu, Xiaoxia ; Chen, Longhua ; Cao, Jian. / miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14. In: Cancer Research. 2015 ; Vol. 75, No. 13. pp. 2674-2685.
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