MicroRNA-9501 inhibits breast cancer proliferation and metastasis through regulating Wnt/β-catenin pathway.

OBJECTIVE

This research was designed to explore the expression characteristics of microRNA-9501 in breast cancer (BCa), and to further explore whether it can influence the development of BCa through the regulation of Wnt/β-Catenin pathway.

PATIENTS AND METHODS

QPCR was carried out to examine microRNA-9501 level in tumor tissue samples and paracancerous ones collected from 42 BCa patients, and the interplay between microRNA-9501 expression and the clinical indicators, as well as the prognosis of BCa patients were analyzed. In addition, we detected microRNA-9501 expression in BCa cell lines by qPCR. Subsequently, microRNA-9501 overexpression model was constructed in BCa cell lines MCF-7 and MDA-MB-231. Then, CCK-8, EdU, cell wound healing, as well as transwell assays, were carried out to evaluate the impact of microRNA-9501 on the biological functions of BCa cells. Finally, the Dual-Luciferase reporting test and tumor formation experiment in nude mice were conducted to further clarify the potential molecular mechanism.

RESULTS

QPCR results indicated that microRNA-9501 level in tumor tissue specimens of BCa patients was remarkably higher than that in adjacent ones, and the difference was statistically significant. Compared with patients with high expression of microRNA-9501, patients with lowly-expressed microRNA-9501 had higher tumor stage, higher incidence of lymph node or distant metastasis, and lower overall survival rate. In addition, compared with control group, cells in microRNA-9501 overexpression group showed a significant decrease in proliferation rate, invasiveness, and migration ability. Meanwhile, luciferase reporting assay revealed that overexpression of β-Catenin remarkably attenuated the luciferase activity of the vector containing wild-type microRNA-9501 sequences, further demonstrating that microRNA-9501 can be targeted by β-Catenin. Meanwhile, qPCR revealed a negative association between β-Catenin and microRNA-9501 in BCa tissues. Finally, tumor-bearing experiments in nude mice also demonstrated that microRNA-9501 may suppress the malignant growth of breast tumor.

CONCLUSIONS

MicroRNA-9501 expression was found remarkably decreased in BCa tissues and cell lines, which was closely relevant to the pathological stage, metastasis incidence, and prognosis of BCa patients. In addition, microRNA-9501 may suppress the malignant progression of BCa via modulating Wnt/β-Catenin path-way.