Background
Breast cancer is the most common female malignancy with high invasion and metastasis abilities. Studies have shown that long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) is an oncogene and is positively correlated with progression and metastasis of breast tumors. However, the detailed mechanism of PVT1 in breast cancer tumorigenesis is not fully understood.
Conclusion
Knockdown of PVT1 repressed breast cancer cell growth and motility, and induced apoptosis in vitro and reduced tumor volume and weight in vivo. Mechanically, the overexpression of PVT1 enhanced TRPS1 level by negatively targeted miR-543 in breast cancer.
Methods
Real-time polymerase quantitative chain reaction (RT-qPCR) was performed to identify the expression levels of PVT1, miR-543 and trichorhinophalangeal syndrome-1 gene (TRPS1) in breast cancer tissues and cells. Cell proliferation was measured by plate clone formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay. Apoptosis and motility of MCF-7 and MDA-MB-436 cells were assessed with flow cytometry assay and transwell migration and invasion analyses, respectively. In addition, a model was established to probe the function of PVT1 silencing in vivo. The target relationship among PVT1, miR-543 or TRPS1 was confirmed by dual-luciferase reporter analysis, RNA immunoprecipitation (RIP) and RNA pull down assays. The protein expression level of TRPS1 was evaluated with Western blot assay.
Results
PVT1 expression was upregulated in breast cancer tissues and cell lines. In addition, PVT1 silencing inhibited breast cancer cell growth and motility, while increased apoptosis. Meanwhile, the effects of PVT1 or miR-543 could be reversed by introducing overexpressed plasmid of miR-543 or TRPS1 in breast cancer cell lines, respectively.