Enforced expression of hsa-miR-125a-3p in breast cancer cells potentiates docetaxel sensitivity via modulation of BRCA1 signaling
- Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province (China)
- Xi'an Health Management Service Center, Xi'an 710032, Shaanxi Province (China)
Epigenetic gene inactivation by microRNAs (miRNAs) plays a key role in malignant transformation, prevention of apoptosis, drug resistance and metastasis. It has been shown that miR-125a is down-regulated in HER2-amplified and HER2-overexpressing breast cancers (BCa), and this miRNA is believed to serve as an important tumor suppressor. miR-125a has two mature forms: hsa-miR-125a-3p and hsa-miR-125a-5p. However, the functional details of these miRNAs in BCa, particularly during pathogenesis of drug resistance, remain largely unexplored. Herein, we reported that hsa-miR-125a-3p expression was significantly reduced in chemoresistant BCa tissues and in experimentally established chemoresistant BCa cells. hsa-miR-125a-3p knockdown promoted cell proliferation and compromised docetaxel (Dox)-induced cell death, whereas overexpression of hsa-miR-125a-3p attenuated Dox chemoresistance in BCa cells. From a mechanistic standpoint, hsa-miR-125a-3p directly targeted 3’-untranslated regions (3′-UTRs) of breast cancer early onset gene 1 (BRCA1) and inhibits its protein expression via translational repression mechanism. In addition, suppression of BRCA1 expression by siRNA treatment effectively improved hsa-miR-125a-3p deficiency-triggered chemoresistance in BCa cells. Collectively, these findings suggest that hsa-miR-125a-3p may function as a tumor suppressor by regulating the BRCA1 signaling, and reintroduction of hsa-miR-125a-3p analogs could be a potential adjunct therapy for advanced/chemoresistant BCa. - Highlights: • hsa-miR-125a-3p expression is downregulated in chemoresistant BCa cells. • hsa-miR-125a-3p knockdown compromises docetaxel-induced cell death in BCa cells. • Overexpression of hsa-miR-125a-3p attenuates Dox chemoresistance in BCa cells. • hsa-miR-125a-3p directly targets the 3′UTR of BRCA1.
- OSTI ID:
- 22696672
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 479, Issue 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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