如何预防和治疗乳腺癌骨转移是当前临床亟待解决的问题。LncRNA FGF14-AS2为FGF14基因第一个内含子的天然反义转录物（NAT），其表达下调与乳腺癌转移密切相关，但具体作用及机制尚不清楚。本课题组前期实验结果表明：过表达FGF14-AS2和FGF14均明显抑制乳腺癌细胞的迁移和侵袭，过表达FGF14-AS2上调FGF14的蛋白表达，但对其mRNA表达和蛋白稳定性均无影响；过表达FGF14-AS2还下调破骨细胞分化促进因子PTHrP和IL-8的表达；FGF14-AS2定位于细胞质并与真核翻译起始因子eIF4E相结合。由此我们推测：FGF14-AS2通过与eIF4E结合在翻译水平调控FGF14的表达，进而抑制乳腺癌骨转移。本项目拟通过细胞、动物和临床水平的研究对此假说进行验证。该项目的研究结果不仅有助于乳腺癌骨转移的分子机制的进一步阐明，也将为乳腺癌骨转移的预防和治疗提供新的靶点。

At present, how to prevent and control the bone metastasis of breast cancer is an urgent problem to be solved in clinic. Natural antisense transcripts (NATs) are a class of very important molecules involved in the regulation of gene expression. LncRNA FGF14-AS2 is a NAT of the first intron of FGF14 gene, and its downregulation is closely related to the metastasis of breast cancer. However, the precise roles and the underlying mechanisms of FGF14-AS2 in the metastasis of breast cancer still need to be explored further. The preliminary data of our group showed that both FGF14-AS2 and FGF14 inhibited the migration and invasion of breast cancer cells when the expression of these two genes was elevated. In addition, FGF14-AS2 overexpression increased the protein level of FGF14, but had no effects on the mRNA expression and protein stability of FGF14. More importantly, we found that the expression of PTHrP and IL-8, which are important stimulating factors for osteoclast differentiation, was decreased by FGF14-AS2 overexpression. Moreover, FGF14-AS2 was demonstrated to be located in the cytoplasm of breast cancer cells and bound with eIF4E, a eukaryotic translation initiation factor. Based on these findings, we postulate that FGF14-AS2 may regulate the expression of FGF14 at the translational level by binding with eIF4E, which further inhibits the bone metastasis of breast cancer. We will test this hypothesis by performing cell biological experiments, construction of bone metastasis model in mice as well as carrying out clinical investigations. Results of this project will not only be helpful in the elucidation of the molecular mechanisms of the bone metastasis of breast cancer further, but also provide a new target for the prevention and treatment of the bone metastasis of breast cancer.