Hongming Song, Dengfeng Li, Tianqi Wu, Dan Xie, Kaiyao Hua, Jiashu Hu, Xiaochong Deng, Changle Ji, Yijun Deng, and Lin Fang. BMB Reports 2018;51:602-7. https://doi.org/10.5483/BMBRep.2018.51.11.168

The aim of the present study was to define the function of microRNA‑424‑5p (miR‑424) in breast cancer cells. The present study investigated the level and the potential function of miR‑424 in breast cancer by reverse transcription‑quantitative polymerase chain reaction assays. miR‑424 expression was decreased in the majority of human breast cancer specimens and cell lines used in the present study. The MTT assay, plate colony formation assay and flow cytometry analyses were used to characterize the function of miR‑424 in two types of breast cancer cell lines. Upregulation of miR‑424 inhibited cellular proliferation and regulated the cell cycle by arresting cells in the G2/M cell phase. The dual‑luciferase reporter assay was used to confirm the direct association between miR‑424 and cyclin‑dependent kinase 1 (CDK1). Silencing of CDK1 expression by CDK1 short interfering RNA also significantly suppressed cell proliferation and arrested cells in the G2/M cell phase. The results of the present study indicated that miR‑424 can suppress cell proliferation and arrest cells in G2/M cell phase by negatively regulating CDK1 mRNA in human breast cancer, possibly through the Hippo pathway and the extracellular signal‑regulated kinase pathway. The results of the present study provided novel evidence for the role of miR‑424 in breast cancer.

Background/Aims: Dysregulated expression of WW domain-binding protein 2 (WBP2) is associated with poor prognosis in ER+ breast cancer patients. However, its role in triple negative breast cancer (TNBC) has not been previously assessed. Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells. Methods: qRT-PCR, western blotting, and immunohistochemical staining were used to evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA-MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR-613 mimics, or miR-613 inhibitors were subject to assays for cell viability, apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting or qRT-PCR were employed to monitor changes in signaling pathway-related genes and proteins. Luciferase assays were performed to assess whether WBP2 is a direct target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo using mouse xenograft models. Results: The expression of WBP2 was upregulated in TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67 in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to the 3’-untranslated region (3’-UTR) of WBP2 and regulated the expression of WBP2. Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613. Conclusion: WBP2 overexpression is associated with the poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt signaling pathway.