MicroRNA-548c-5p inhibits the proliferation of breast cancer cells through regulating Wnt/β-catenin signaling pathway

S.-Z. He, Q. Wang

Department of Oncology, Baoan Central Hospital of Shenzhen, the 5th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China. heshaozhong8@126.com

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• Oncology

OBJECTIVE: The aim of this study was to explore the function of microRNA-548c-5p in breast cancer (BCa) and the underlying mechanism. Our findings might help to provide a theoretical basis for the diagnosis and treatment of BCa.

PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression level of microRNA-548c-5p in BCa tumor tissues and para-cancerous tissues. The relationship between microRNA-548c-5p expression and clinical indicators of BCa was analyzed. Meanwhile, the expression of microRNA-548c-5p in the BCa cells was detected by qRT-PCR as well. MicroRNA-548c-5p overexpression and the knockdown models were constructed in BCa cell lines MCF-7 and MDA-MB-231. Subsequently, Cell Counting Kit-8 (CCK-8), colony formation and 5-ethynyl-2’-deoxyuridine (EdU) assays were performed to analyze the influence of microRNA-548c-5p on biological functions of BCa cells. Finally, the interaction between microRNA-548c-5p and Wnt/b-catenin signaling pathway was investigated.

RESULTS: QRT-PCR results showed that the expression level of microRNA-548c-5p in BCa tumor tissues was remarkably lower than that of adjacent tissues, and the difference was statistically significant (p<0.05). Compared with patients with high expression of microRNA-548c-5p, the pathological stage of patients with low microRNA-548c-5p expression was significantly higher (p<0.05). Similarly, microRNA-548c-5p overexpression remarkably decreased the proliferation ability of BCa cells in vitro. However, microRNA-548c-5p knockdown showed an opposite trend. In addition, Wnt1, a key factor in the Wnt/b-catenin signaling pathway, was found remarkably up-regulated in BCa cell lines and tissues. Wnt1 expression was negatively correlated with microRNA-548c-5p expression. Western Blotting results demonstrated that microRNA-548c-5p mimics remarkably down-regulated the levels of the proteins in the Wnt/b-catenin signaling pathway. Conversely, opposite results were observed in microRNA-548c-5p inhibitor group. The rescue experiments in the cells revealed that there might be a mutual regulation between microRNA-548c-5p and Wnt1, thereby together regulating the malignant growth of BCa.

CONCLUSIONS: MicroRNA-548c-5p was lowly expressed in BCa tissues and cells, which was closely related to the pathological stage of BCa. In addition, microRNA-548c-5p significantly inhibited the proliferation of BCa cells via modulating Wnt/b-catenin signaling pathway.

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