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Title: MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression aremore » closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.« less
Authors:
 [1] ;  [2] ; ; ; ;  [3] ;  [4] ;  [3] ;  [5] ;  [4] ;  [2]
  1. Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 (China)
  2. (China)
  3. State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an (China)
  4. State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an (China)
  5. Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 (China)
Publication Date:
OSTI Identifier:
22462159
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 463; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACCURACY; BIOLOGICAL MARKERS; CELL PROLIFERATION; CHEMOTHERAPY; CLASSIFICATION; INHIBITION; MAMMARY GLANDS; MESSENGER-RNA; METASTASES; MOLECULES; NEOPLASMS; PATIENTS; PHENOBARBITAL; PLANT GROWTH; PROTEINS; SPECIFICITY