LRRFIP1基因经Wnt通路参与骨髓增生异常综合征发病机制的研究

Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic disorders, with the characteristics of diagnostic difficulties and poor prognosis, so it would be of great significance to explore the pathogenesis and to look for new targets of diagnosis and treatment for MDS. The previous study of our team showed that the abnormal activation of the canonical Wnt signaling pathway, and LRRFIP1 can interact with Dvls in Wnt signaling pathway according to the literature reports. So we hypothesize that LRRFIP1 can participate in the pathogenesis of MDS via Wnt signaling pathway. We will identify the interaction between LRRFIP1 and Dvls through the Co-IP technology and TOPflash/FOP flash assay, and then using the methods of TOPflash/FOP flash assay, qRT-PCR, RNA interference and Western blot in MDS cell lines to determine the impact of LRRFIP1 expression level on the activation of the Wnt signaling pathway. And at the same time we observe the biological characteristics of the cell line. Meanwhile, we will validate that LRRFIP1 impacts on the activation of the Wnt signaling pathway. Eventually, we will infer the mechanisms of LRRFIP1 involved in the development of MDS via the Wnt signaling pathway by interacting with Dvls, and provide new therapeutic targets for MDS.

骨髓增生异常综合征(MDS)是一类高度异质性的疾病，诊断难、预后差，探索MDS的发病机制、寻找诊断、治疗新靶点具有重要意义。课题组前期研究发现经典Wnt通路异常激活参与MDS的发生发展，结合文献报道，LRRFIP1可与Wnt通路中的Dvls蛋白相互作用；推测LRRFIP1通过调控Wnt信号通路参与MDS的发生发展。本研究拟通过Co-IP技术和荧光素酶试验观察LRRFIP1与Dvls的相互作用，再通过荧光素酶试验、qRT-PCR、RNA干扰技术、Western blot技术在MDS细胞系中确定LRRFIP1表达水平对Wnt信号通路活性的影响，并同时观察对细胞系细胞生物学特性的影响。同时在随访资料完整的MDS患者骨髓标本中验证LRRFIP1调控Wnt信号通路，证实LRRFIP1通过与Dvls相互作用参与Wnt信号通路促进MDS的发生发展，为MDS新的治疗靶点提供依据。

骨髓增生异常综合征(MDS)是一类高度异质性的疾病，诊断难、预后差，探索MDS的发病机制、寻找诊断、治疗新靶点具有重要意义。课题组前期研究发现经典Wnt通路异常激活参与MDS的发生发展，结合文献报道，LRRFIP1可与Wnt通路中的Dvls蛋白相互作用；推测LRRFIP1通过调控Wnt信号通路参与MDS的发生发展。本研究通过Co-IP技术证实LRRFIP1与Dvls之间存在相互作用，通过荧光素酶试验证实LRRFIP1表达水平影响Wnt信号通路活性，同时影响细胞生物学特性。在MDS患者骨髓标本中验证LRRFIP1调控Wnt信号通路，证实LRRFIP1通过与Dvls相互作用参与Wnt信号通路促进MDS的发生发展，为MDS新的诊断及治疗靶点提供依据。