OncoTargets and Therapy (Jun 2019)
MicroRNA-937 inhibits the malignant phenotypes of breast cancer by directly targeting and downregulating forkhead box Q1
Abstract
Xiaoting Han,1 Xiaolong Guo,2 Wenzhen Zhang,3 Qiumei Cong41Department of Breast Surgery, Weihai Central Hospital, Shandong 264400, People’s Republic of China; 2Department of Breast Surgery, Zibo Maternity and Child Health Hospital, Shandong 255020, People’s Republic of China; 3Department of Breast Surgery, Rizhao Central Hospital, Shandong 276801, People’s Republic of China; 4Department of Oncology, Weihai Central Hospital, Shandong 264400, People’s Republic of ChinaPurpose: Numerous microRNAs (miRNAs) are aberrantly expressed in breast cancer, and the dysregulation of miRNAs may affect the aggressiveness of this cancer. Aberrant expression of miRNA-937 (miR-937) in gastric and lung cancers has been reported, which plays tumor-suppressive or oncogenic roles in carcinogenesis including cancer progression. Our purpose was to investigate the involvement of miR-937 in breast cancer progression.Patients and methods: The expression profile of miR-937 in breast cancer was assessed by reverse-transcription quantitative PCR. Biological effects of miR-937 upregulation on the malignant characteristics of breast cancer cells were determined in a series of functional experiments. The direct target of miR-937 in breast cancer cells was also identified.Results: Herein, the expression levels of miR-937 were notably lower in breast cancer, and its underexpression was significantly correlated with lymph node metastasis and TNM stage. Patients with breast cancer underexpressing miR-937 showed shorter overall survival than did patients with breast cancer overexpressing miR-937. Proliferation, migration, and invasiveness of breast cancer cells were evidently suppressed by miR-937 upregulation. In addition, ectopic miR-937 expression hindered breast cancer tumor growth in vivo. Forkhead box Q1 (FOXQ1) mRNA was found to be a direct target of miR-937 in breast cancer. FOXQ1 turned out to be overexpressed in breast cancer tissues, and its overexpression negatively correlated with miR-937 expression. Moreover, silencing of FOXQ1 recapitulated the tumor-suppressive effects of miR-937 overexpression on breast cancer cells. Notably, FOXQ1 restoration abrogated the miR-937-mediated suppression of proliferation, migration, and invasiveness of breast cancer cells.Conclusion: These results collectively revealed that miR-937 acts as a tumor suppressor in breast cancer and restrains cancer progression by directly targeting FOXQ1 mRNA. These data suggest that targeting of the novel miR-937–FOXQ1 axis is an attractive therapeutic method against breast cancer.Keywords: breast cancer, microRNA-937, forkhead box Q1
