骨转移是乳腺癌的主要转移方式，寻找其关键调控因子并阐明其作用机制对乳腺癌的诊治具有重要意义。我们在前期研究中发现：长链非编码RNA-PVT1在骨转移性乳腺癌组织中显著高表达，并且与乳腺癌患者骨转移密切相关；下调PVT1有效抑制乳腺癌“干细胞样特性”、侵袭、迁移、和体内骨转移。进一步预实验结果显示PVT1可：①结合E3泛素化连接酶TMF1而抑制STAT3的泛素化降解；②作为ceRNA吸附并解除多个miRNA对IL-6表达的抑制，促进其分泌；从而促进骨转移相关通路IL-6/STAT3的激活。然而，PVT1促进乳腺癌骨转移的详细分子机制仍不清楚。本项目将综合采用生物信息学、分子生物学和细胞生物学等研究手段，深入探讨PVT1是否驱动乳腺癌骨转移并阐明其中详细的分子机制，为lncRNA调控乳腺癌骨转移提供新的理论依据，并为乳腺癌的临床诊治提供新的靶标。

Bone is the common site of metastasis in breast cancer. Thus, a better understanding of the molecular mechanisms and key regulators involved in breast cancer bone metastasis are necessary in order to develop more effective therapeutics for this disease. In the previous study, we found that long non-coding RNA PVT1 was highly expressed in skeletal metastatic breast cancer tissues, and high expression of long non-coding RNA PVT1 was significantly associated with very poor bone metastasis-free survival. Knockdown of PVT1 expression inhibited the stem cell-like properties, invasion and migration in breast cancer cells, and bone metastasis in vivo. Moreover, we found that PVT1 could inhibit ubiquitin-mediated degradation of STAT3 through binding E3 ubiquitin ligase TMF1, and promote the synthesis and secretion of IL-6 by serving as a ceRNA to inhibit the function of various miRNAs targeting IL-6, thereby promoting constitutive activation of bone metastasis-related IL-6/STAT3 signaling pathway. Based on the above findings, in this study, we will further demonstrate whether PVT1 could drive breast cancer bone metastasis and find out its precise molecular mechanism, by utilizing various research methods such as bioinformatics, molecular biology and cell biology, in order to provide a new diagnostic biomarkers and therapeutic target for breast cancer bone metastasis.