BMP9下调SNHG3抑制BCC与BMSC相互作用的研究

在已观察到BMP9能抑制乳腺癌细胞及其骨微环境基础上，经基因芯片技术发现BMP9能使乳腺癌细胞SNHG3表达下调，综合前期实验结果、生物信息学分析及文献报道，推测：SNHG3表达下调后，一方面减少与UPF1结合，抑制TGF-β/Smad活性，另一方面减少与ZEB1的竞争性结合miR-186-5p，抑制EMT相关通路，减弱BCC与BMSC相互作用，促进BMSC成骨，抑制BCC侵袭能力。为证实该假说，本课题拟以BCC及BMSC细胞为研究对象，利用细胞共培养、FISH、质谱、CHIP、小鼠骨转移模型等技术，从体内体外两个层面，研究BMP9下调SNHG3对BCC与BMSC交互对话、BMSC成骨分化、骨吸收、及BCC骨转移能力等的影响及其分子机制。本课题在前期基础上探讨SNHG3介导下BMP9抑制乳腺癌骨微环境的分子机制，为阐明BMP9的抑瘤机制、开发BMP9治疗乳腺癌骨转移的新用途提供实验基础。

In our previous date, it is showed that BMP9 can inhibit breast cancer cells and their microenvironment. Furtherly, we found that BMP9 can decrease the expression of SNHG3 in breast cancer cells by LncRNA microarray. On the basis of bioinformatics analysis results and other data, we hypothesized that BMP9 inhibit the interaction of BCC with BMSC, promote the induction of osteogenesis of BMSC and attenuate the bone metastasis ability of BCC by downregulating SNHG3，through inhibiting TGF-β/Smad signaling pathway via reducing integration with UPF1, and reducing competitive binding to ZEB1 to miR-186-5p , which may inhibit EMT pathway by ZEB1. In order to confirm this hypothesis, BCC and BMSC cells are used as research objects, cell co-culture, FISH, mass spectrometry, CHIP, mouse bone metastasis model are utilized to reveal the mechanism of BMP9 on BCC and BMSC interaction, BMSC osteogenic differentiation status, bone resorption status, and BCC bone metastasis ability by downregulation of SNHG3. The project intends to explore the molecular mechanism of BMP9 inhibiting bone microenvironment in breast cancer mediated by SNHG3, providing an important experimental basis for elucidating the molecular mechanism of BMP9 inhibiting bone metastasis of breast cancer and developing new applications of BMP9 in the treatment of osteolytic metastasis of breast cancer.