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MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt
Yuying Zhao1, Weifeng Pang1, Ning Yang1
1Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Abstract:
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.
Insights
MicroRNA-511 (miR-511) is downregulated in breast cancer, inhibiting tumor progression. Restoring miR-511 suppresses cancer growth and metastasis by targeting SOX9 and the PI3K/Akt pathway, suggesting miR-511 as a therapeutic target.
Area of Science:
- Molecular Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are key regulators in cancer development, with specific miRNAs showing altered expression in breast cancer.
- The role and expression of microRNA-511 (miR-511) in breast cancer remain largely uncharacterized, necessitating further investigation.
Purpose of the Study:
- To determine the expression levels of miR-511 in breast cancer tissues and cell lines.
- To elucidate the functional role of miR-511 in breast cancer progression.
- To identify downstream target genes of miR-511 and its associated signaling pathways.
Main Methods:
- Quantitative real-time PCR was used to assess miR-511 expression in breast cancer tissues and cell lines.
- In vitro and in vivo assays were performed to evaluate the effects of miR-511 restoration on cancer cell proliferation, apoptosis, metastasis, and tumor growth.
- Western blotting and luciferase reporter assays were employed to validate SOX9 as a direct target of miR-511 and to analyze the PI3K/Akt signaling pathway.
Main Results:
- miR-511 expression was significantly downregulated in breast cancer tissues and cell lines, correlating with advanced tumor stage and lymph node metastasis.
- Overexpression of miR-511 suppressed breast cancer cell proliferation, colony formation, and metastasis, while promoting apoptosis in vitro and inhibiting tumor growth in vivo.
- SRY-box 9 (SOX9) was identified as a direct target of miR-511, with its expression inversely correlated to miR-511 levels. miR-511 targeted SOX9 to inhibit the PI3K/Akt pathway.
Conclusions:
- miR-511 acts as a tumor suppressor in breast cancer by targeting SOX9 and deactivating the PI3K/Akt signaling pathway.
- The downregulation of miR-511 contributes to breast cancer progression, highlighting its potential as a diagnostic marker and therapeutic target.
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