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Updated: Jan 22, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
miR-516a-3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway
Yanyan Chi1, Feng Wang1, Tengfei Zhang1
1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
miR-516a-3p has been reported to play a suppressive role in several types of human tumours. However, the expression level, biological function and fundamental mechanisms of miR-516a-3p in breast cancer remain unclear. In the present study, we found that miR-516a-3p expression was down-regulated and Pygopus2 (Pygo2) expression was up-regulated in human breast cancer tissues and cells. Through analysing the clinicopathological characteristics, we demonstrated that low miR-516a-3p expression or positive Pygo2 expression was a predictor of poor prognosis for patients with breast cancer. The results of a dual luciferase reporter assay and Western blot analysis indicated that Pygo2 was a target gene of miR-516a-3p. Moreover, overexpression of miR-516a-3p inhibited cell growth, migration and invasion as well as epithelial-mesenchymal transition (EMT) of breast cancer cells, whereas reduced miR-516a-3p expression promoted breast cancer cell growth, migration, invasion and EMT. Furthermore, we showed that miR-516a-3p suppressed cell proliferation, metastasis and EMT of breast cancer cells by inhibiting Pygo2 expression. We confirmed that miR-516a-3p exerted an anti-tumour effect by inhibiting the activation of the Wnt/β-catenin pathway. Finally, xenograft tumour models were used to show that miR-516a-3p inhibited breast cancer cell growth and EMT via suppressing the Pygo2/Wnt signalling pathway. Taken together, these results show that miR-516a-3p inhibits breast cancer cell growth, metastasis and EMT by blocking the Pygo2/ Wnt/β-catenin pathway.
Insights
MicroRNA-516a-3p (miR-516a-3p) suppresses breast cancer growth and metastasis by inhibiting Pygopus2 (Pygo2) and the Wnt/β-catenin pathway. Down-regulation of miR-516a-3p and up-regulation of Pygo2 predict poor prognosis in breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-516a-3p (miR-516a-3p) is implicated in tumor suppression, but its role in breast cancer is not fully understood.
- The expression patterns and functional mechanisms of miR-516a-3p in breast cancer require further investigation.
Purpose of the Study:
- To elucidate the expression, function, and regulatory mechanisms of miR-516a-3p in breast cancer.
- To investigate the relationship between miR-516a-3p, Pygopus2 (Pygo2), and the Wnt/β-catenin pathway in breast cancer progression.
Main Methods:
- Quantitative real-time PCR and Western blot analysis to assess gene and protein expression.
- Dual luciferase reporter assay to confirm direct targeting.
- Cell proliferation, migration, and invasion assays.
- Epithelial-mesenchymal transition (EMT) analysis.
- Xenograft tumor models in mice.
Main Results:
- miR-516a-3p was significantly down-regulated, while Pygo2 was up-regulated in breast cancer tissues and cells.
- Low miR-516a-3p or high Pygo2 expression correlated with poor patient prognosis.
- Pygo2 was identified as a direct target of miR-516a-3p.
- miR-516a-3p overexpression inhibited breast cancer cell growth, migration, invasion, and EMT, whereas its down-regulation promoted these processes.
- miR-516a-3p suppressed breast cancer progression by inhibiting Pygo2 and subsequently activating the Wnt/β-catenin pathway.
- In vivo studies confirmed that miR-516a-3p inhibits tumor growth and EMT via the Pygo2/Wnt signaling pathway.
Conclusions:
- miR-516a-3p acts as a tumor suppressor in breast cancer by targeting Pygo2 and inhibiting the Wnt/β-catenin pathway.
- Restoring miR-516a-3p levels may offer a therapeutic strategy for breast cancer treatment.
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