LncRNA- n384480介导乳腺癌细胞迁移及重塑骨转移微环境的机制研究

Bone metastasis frequently develops years after the initiation of primary breast tumor. The mechanism of LncRNAs involved in bone metastasis remains unclear. Through a novel mouse model using human-derived orthotopic breast tissue, metastatic bone, and breast cancer cell lines, our previous studies have showed lncRNA-n384480 was tightly related with bone metastasis in breast cancer. High n384480 expression correlated with bone metastasis and poor prognosis in breast cancer patients. Upregulation of n384480 promoted the migration and invasion capacity of breast cancer cells. Moreover, breast cancer cells that carried high levels of the n384480, thereby promoting HMSC differentiation into osteoclasts and remodel bone metastasis microenvironment. MicroRNA-1224-3p can bind with n384480 to regulate the downstream MAPK signal pathway. But the mechanism is unclear. In combination with molecular level, cell lines, patients’ specimens and animal model, we plan to investigate the mechanism of “lncRNA n384480-microRNA-1224-3p-MAPK” pathway promoting migration and invasion of breast cancer cells; explore the effects of HMSC differentiation and osteoclast formation and reveal the mechanism of remodeling bone metastasis microenvironment. It is expected to provide a theoretical basis of the molecular targeted therapy for breast cancer bone metastasis.

LncRNA在乳腺癌骨转移中尚未得到深入研究。我们通过“人源性乳腺癌骨转移小鼠模型”，首次筛选出乳腺癌骨转移相关lncRNA-n384480。体外细胞实验和临床标本证实：n384480促进乳腺癌细胞迁移、侵袭；与乳腺癌骨转移发生率正相关；促进HMSC分化为破骨细胞与骨转移处微环境密切相关。microRNA-1224-3p靶向调控n384480进而调节下游的MAPK信号通路。但具体机制不清。据此拟从分子、细胞、组织以及动物水平等多层次明确乳腺癌细胞中“lncRNA n384480- microRNA-1224-3p-MAPK”信号通路促进迁移侵袭，促进HMSC分化为破骨细胞，重塑骨转移微环境的作用机理，有望为乳腺癌骨转移的分子靶向治疗提供新的理论基础。

LncRNA在乳腺癌骨转移中尚未得到深入研究。我们通过“人源性乳腺癌骨转移小鼠模型”.，首次筛选出乳腺癌骨转移相关lncRNA-n384480。体外细胞实验和临床标本证实：n384480促.进乳腺癌细胞迁移、侵袭；与乳腺癌骨转移发生率正相关；促进HMSC分化为破骨细胞与骨转移.处微环境密切相关。microRNA-1224-3p靶向调控n384480进而调节下游的MAPK信号通路。但具.体机制不清。据此拟从分子、细胞、组织以及动物水平等多层次明确乳腺癌细胞中“lncRNA n.384480- microRNA-1224-3p-MAPK”信号通路促进迁移侵袭，促进HMSC分化为破骨细胞，重塑.骨转移微环境的作用机理，有望为乳腺癌骨转移的分子靶向治疗提供新的理论基础。