期刊
ONCOTARGET
卷 7, 期 17, 页码 24076-24087出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8119
关键词
MiR-1229; breast cancer; proliferation; Wnt/beta-catenin pathway
资金
- Ministry of Science and Technology of China grant (973 Program) [2014CB910604]
- Natural Science Foundation of China [81530082, 91529301, 81572228, 81325013, 51201546, 81272196, 81272198]
- Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS)
- Fundamental Research Funds for the Central Universities [12ykpy25]
- Foundation of Key Laboratory of Gene Engineering of the Ministry of Education
Constitutive activation of the Wnt/beta-catenin pathway promotes malignant proliferation and it is inversely correlated with the prognosis of patients with breast cancer. However, mutations in key regulators, such as APC, Axin and beta-catenin, contribute to aberrant activation of the Wnt/beta-catenin signaling pathway in various cancers, but rarely found in breast cancer, suggesting that other mechanisms might be involved in the activation of Wnt/beta-catenin signaling in breast cancer. In the present study, we found that miR-1229 expression was markedly upregulated in breast cancer and associated with poor survival. Overexpressing miR-1229 promoted while inhibiting miR-1229 reduced, proliferation of breast cancer cell proliferation in vitro and tumor growth in vivo. Furthermore, we found that overexpression of miR-1229 activated the Wnt/beta-catenin signaling pathway in breast cancer by directly targeting the multiple important negative regulators of Wnt/beta-catenin signaling, including adenomatous polyposis coli (APC), glycogen synthase kinase-3 beta (GSK-3 beta), and inhibitor of beta-catenin and T cell factor (ICAT). Taken together, our results suggest that miR-1229 plays an important role in promotion breast cancer progression and may represent a novel therapeutic target in breast cancer.
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