MiR-591 functions as tumor suppressor in breast cancer by targeting TCF4 and inhibits Hippo-YAP/TAZ signaling pathway

Cancer Cell Int. 2019 Apr 24;19:108. doi: 10.1186/s12935-019-0818-x. eCollection 2019.

Abstract

Background: MicroRNAs have been involved in regulating crucial biological function in some tumors. However, the clinical role and functional effects of miR-591 in breast cancer remain unknown.

Methods: The expression of miR-591 was detected in breast cancer tissues and their paired normal tissues by qRT-PCR. Functional assays were performed to confirm the effects of miR-591 on the proliferation and invasion of breast cancer. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro assays were used to confirm that TCF4 was a target gene of miR-591. Western blot analysis was carried out to analyze the relationship between miR-591 expression and YAP1 expression in breast cancer.

Results: We found that miR-591 expression levels were significantly downregulated in breast cancer tissues compared to adjacent normal tumor tissues. Lower miR-591 expression notably related to lymph node metastasis and advanced TNM stage in patients with breast cancer. In vitro, cell proliferation and invasion were inhibited by transfection of miR-591 mimic in breast cancer cells, but were promoted by transfection of miR-591 inhibitor, compared to the controls. In vivo, we also found that miR-591 mimic significantly inhibited cell proliferation ability. Moreover, we identified that TCF4 was a direct target of miR-591 in breast cancer. TCF4 mediated the inhibiting effects of miR-591 on cell proliferation and invasion in breast cancer cells. In additional, we revealed that miR-591 overexpression significantly inhibited the Hippo-YAP/TAZ signaling pathway in breast cells by downregulated YAP1 expression in breast cells.

Conclusion: Together, these results indicated that miR-591 is downregulated in breast cancer and could act as a potential target of breast cancer treatment.

Keywords: Breast cancer; MicroRNAs; TCF4; YAP1; miR-591.