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MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer.

Publication ,  Journal Article
Xu, X; Zhang, Y; Jasper, J; Lykken, E; Alexander, PB; Markowitz, GJ; McDonnell, DP; Li, Q-J; Wang, X-F
Published in: Oncotarget
April 12, 2016

Triple-negative breast cancer (TNBC) presents a major challenge in the clinic due to its lack of reliable prognostic markers and targeted therapies. Accumulating evidence strongly supports the notion that microRNAs (miRNAs) are involved in tumorigenesis and could serve as biomarkers for diagnostic purposes. To identify miRNAs that functionally suppress metastasis of TNBC, we employed a concerted approach with selecting miRNAs that display differential expression profiles from bioinformatic analyses of breast cancer patient databases and validating top candidates with functional assays using breast cancer cell lines and mouse models. We have found that miR-148a exhibits properties as a tumor suppressor as its expression is inversely correlated with the ability of both human and mouse breast cancer cells to colonize the lung in mouse xenograft tumor models. Mechanistically, miR-148a appears to suppress the extravasation process of cancer cells, likely by targeting two genes WNT1 and NRP1 in a cell non-autonomous manner. Importantly, lower expression of miR-148a is detected in higher-grade tumor samples and correlated with increased likelihood to develop metastases and poor prognosis in subsets of breast cancer patients, particularly those with TNBC. Thus, miR-148a is functionally defined as a suppressor of breast cancer metastasis and may serve as a prognostic biomarker for this disease.

Duke Scholars

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

April 12, 2016

Volume

7

Issue

15

Start / End Page

20381 / 20394

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Wnt1 Protein
  • Tumor Cells, Cultured
  • Triple Negative Breast Neoplasms
  • Survival Rate
  • Prognosis
  • Neuropilin-1
  • Neoplasm Invasiveness
  • MicroRNAs
  • Mice, Nude
 

Citation

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Xu, X., Zhang, Y., Jasper, J., Lykken, E., Alexander, P. B., Markowitz, G. J., … Wang, X.-F. (2016). MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer. Oncotarget, 7(15), 20381–20394. https://doi.org/10.18632/oncotarget.7953
Xu, Xin, Yun Zhang, Jeff Jasper, Erik Lykken, Peter B. Alexander, Geoffrey J. Markowitz, Donald P. McDonnell, Qi-Jing Li, and Xiao-Fan Wang. “MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer.Oncotarget 7, no. 15 (April 12, 2016): 20381–94. https://doi.org/10.18632/oncotarget.7953.
Xu X, Zhang Y, Jasper J, Lykken E, Alexander PB, Markowitz GJ, et al. MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer. Oncotarget. 2016 Apr 12;7(15):20381–94.
Xu, Xin, et al. “MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer.Oncotarget, vol. 7, no. 15, Apr. 2016, pp. 20381–94. Pubmed, doi:10.18632/oncotarget.7953.
Xu X, Zhang Y, Jasper J, Lykken E, Alexander PB, Markowitz GJ, McDonnell DP, Li Q-J, Wang X-F. MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer. Oncotarget. 2016 Apr 12;7(15):20381–20394.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

April 12, 2016

Volume

7

Issue

15

Start / End Page

20381 / 20394

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Wnt1 Protein
  • Tumor Cells, Cultured
  • Triple Negative Breast Neoplasms
  • Survival Rate
  • Prognosis
  • Neuropilin-1
  • Neoplasm Invasiveness
  • MicroRNAs
  • Mice, Nude