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Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer
- Source :
- Molecular Therapy: Nucleic Acids, Vol 17, Iss, Pp 347-361 (2019), Molecular Therapy. Nucleic Acids
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients. Keywords: breast cancer, circBMPR2, tumor suppressor, tamoxifen resistance, miR-553, USP4
- Subjects :
- 0301 basic medicine
tumor suppressor
tamoxifen resistance
Motility
miR-553
Article
Metastasis
law.invention
03 medical and health sciences
0302 clinical medicine
Breast cancer
breast cancer
law
Drug Discovery
Medicine
skin and connective tissue diseases
Gene knockdown
business.industry
Cell growth
lcsh:RM1-950
circBMPR2
Cancer
medicine.disease
030104 developmental biology
USP4
lcsh:Therapeutics. Pharmacology
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Suppressor
business
Subjects
Details
- Language :
- English
- ISSN :
- 21622531
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy: Nucleic Acids
- Accession number :
- edsair.doi.dedup.....9af8f867e16a0a01ff2524dbee1c8089