科研之友
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摘要
Numerous studies have revealed that a subset of microRNAs (miRNAs) is aberrantly expressed in breast cancer. The dysregulation of miRNAs is involved in the tumorigenesis and progression of breast cancer due to their negative regulation of downstream target genes. Therefore, the identification of deregulated miRNAs in breast cancer may provide important insights into the diagnosis and treatment of patients with this disease. miRNA-511 (miR-511) has been identified to be deregulated in diverse human cancer types; however, neither the expression status nor the detailed roles of miR-511 in breast cancer have been clarified. Thus, it was aimed to determine the expression of miR-511 in breast cancer, examine the role in malignant progression and explore its downstream targets. The results of the present study revealed that the expression of miR-511 was downregulated in breast cancer tissues and cell lines. Decreased expression of miR-511 was significantly associated with lymph node metastasis and tumor stage in patients with breast cancer. Functional analyses revealed that restoring miR-511 expression suppressed breast cancer cell proliferation and colony formation, promoted apoptosis and reduced metastasis in vitro, while it attenuated tumor growth in vivo. Additionally, it was revealed that SRY-box 9 (SOX9) was a direct target gene of miR-511 in breast cancer cells. SOX9 was upregulated in breast cancer tissues and its expression was inversely correlated with that of miR-511. Furthermore, SOX9 inhibition simulated the tumor-suppressive roles of miR-511 overexpression in breast cancer cells, while SOX9 reintroduction partially rescued these effects of miR-511. Notably, the upregulation of miR-511 targeted SOX9 to deactivate the PI3K/Akt signaling in breast cancer in vitro and in vivo. In conclusion, miR-511 was downregulated in breast cancer, and impeded its malignant progression by directly targeting SOX9 and regulating the PI3K/Akt pathway. Thus, miR-511 is a potential therapeutic target in breast cancer.
- 出版日期2018-12
- 单位哈尔滨医科大学
