Let-7b/IL-10在三阴乳腺癌相关成纤维细胞中的功能与机制研究

三阴乳腺癌（TNBC）是一种高度恶性且临床治疗效果及预后极差的乳腺癌亚型。由于三阴乳腺癌细胞基因背景复杂且易于突变，而基因组更稳定的癌相关成纤维细胞(CAFs)将可能成为很有前景的癌症控制和治疗的新靶点。我们的前期研究发现，CAFs在三阴乳腺癌细胞增殖、迁移和侵袭中发挥重要作用，let-7b在CAFs中表达水平明显降低，并且CAFs中高表达let-7b可以降低CAFs的促三阴乳腺癌细胞增殖与侵袭能力。荧光素酶报告实验显示白介素-10 (IL-10)可能是let-7b调控三阴乳腺癌进展的下游靶点。本项目拟在分子、细胞及动物水平，从正反两方面，以CAFs作为新视角，探究其在三阴乳腺癌进展中的功能，并深入研究let-7b/IL-10信号在CAFs促进三阴乳腺癌进展中的作用与机制，为三阴乳腺癌的控制与治疗提供理论新依据。

Triple-Negative Breast Cancer (TNBC) is highly malignant and refractory subtype of breast cancer with poor prognosis. TNBC cells are genetically unstable and mutate frequently, which lead to chemoresistance. Thus, the genetically more stable cancer-associated fibroblasts(CAFs) will probably be the promising target for cancer control and treatment. Our primary studies demonstrated that CAFs played an important role in the proliferation, migration and invasion of TNBC cells. The expression of let-7b was significantly decreased in CAFs of TNBC. Moreover, overexpression of let-7b in CAFs will attenuate the pro-proliferative and proinvasive effects of CAFs on TNBC cells. Furthermore, the luciferase reporter assay displayed that the cytokine interleukin-10(IL-10) was probably the downstream target of let-7b in modulating the progression of TNBC by CAFs. On the level of molecular, cellular and animal assays, this project will explore the function of CAFs in the progression of TNBC and the role and mechanisms of let-7b/IL-10 signal in CAFs-mediated TNBC progression, which will provide a new theoretical basis for CAFs-targeted cancer control and treatment.