Tumor-promoting properties of miR-8084 in breast cancer through enhancing proliferation, suppressing apoptosis and inducing epithelial-mesenchymal transition

• Published in: Journal of translational medicine 2018-02, Vol.16 (1), p.38-38, Article 38
• Main Authors: Gao, Yujing, Ma, Hongning, Gao, Chanchan, Lv, Ye, Chen, XueHua, Xu, Rongrong, Sun, Miao, Liu, Xinrui, Lu, Xiaohong, Pei, Xiuying, Li, Pu
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Animals; Apoptosis - genetics; Base Sequence; bcl-2-Associated X Protein - metabolism; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Carcinogenesis - genetics; Carcinogenesis - pathology; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Clone Cells; Development and progression; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; ING2; MAP Kinase Signaling System; Mice, Inbred BALB C; MicroRNAs - genetics; MicroRNAs - metabolism; miR-8084; Models, Biological; Neoplasm Invasiveness; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Transfection; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumorigenesis; Up-Regulation - genetics; Wound Healing
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-018-1419-5

Breast cancer is one of the most frequent malignancies and the second leading cause of cancer-related mortality in women. MicroRNAs play a key role in breast cancer development and progression. microRNA(miR)-8084 has been observed an aberrant expression in breast cancer. However, the functions and regulatory axes of miR-8084, particularly in breast cancer, were not entirely clear. miR-8084 expression in breast cancer were investigated in a GEO dataset by in silico analysis and in 42 paired tumor tissues by qPCR. The effects of deregulation of miR-8084 on breast cancer cell proliferation, migration and invasion in vitro and tumorigenicity in vivo were examined by colony-formation assay, wound healing assay, transwell assay and nude mouse subcutaneous tumor formation model. The target gene of miR-8084 were predicted by TargetScan and miRDB, and confirmed by luciferase reporter system. The roles of miR-8084 in the breast cancer cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) were investigated by MTS, FACS and associated-marker detection by western blot. miR-8084 is significantly up-regulated in both serum and malignant tissues from the source of breast cancer patients. miR-8084 promotes the proliferation of breast cancer cells by activating ERK1/2 and AKT. Meanwhile miR-8084 inhibits apoptosis by decreasing p53-BAX related pathway. miR-8084 also enhances migration and invasion by inducing EMT. Moreover, the tumor suppressor ING2 is a potential target of miR-8084, and miR-8084 regulatory axes contribute to pro-tumor effect, at least partially through regulating ING2. Our results strongly suggest that miR-8084 functions as an oncogene that promotes the development and progression of breast cancer, and miR-8084 is a potential new diagnostic marker and therapeutic target of breast cancer.