MicroRNA-99a Suppresses Breast Cancer Progression by Targeting FGFR3
Xinghua Long, Yu Shi, Peng Ye, Juan Guo, Qian Zhou, Yueting Tang
Abstract
MicroRNAs have been implicated in acting as oncogenes or anti-oncogenes in breast cancer by regulating diverse cellular pathways. In the present study, we investigated the effects of miR-99a on cell biological processes in breast cancer. breast cancer cells were transfected with a lentivirus that expressed miR-99a or a scramble control sequence.Functional experiments showed that miR-99a reduced breast cancer cell proliferation, invasion and migration. Tumor xenograft experiment suggested miR-99a overexpression inhibited breast cancer cell proliferation in vivo. The dual luciferase assay revealed that miR-99a directly targets FGFR3 by binding its 3' UTR in breast cancer. miR-99a was strongly down-regulated in breast tumor and FGFR3 was significantly up-regulated in breast tumor. FGFR3 silencing inhibited proliferation, migration and invasion of breast cancer cells. Deep sequencing indicated that miR-99a overexpression regulates multiple signaling pathways and triggeres the alteration of the whole transcriptome. We constructed correlated expression networks based on circRNA/miRNA and lncRNA/miRNA competing endogenous RNAs regulation and miRNA-mRNA interaction, which provided new insights into the regulatory mechanism of miR-99a. In conclusion, these results suggest that the miR-99a/FGFR3 axis is an important tumor regulator in breast cancer and might have potential as a therapeutic target.