RNA结合蛋白RNPC1调控乳腺癌ERα表达的机制研究

内分泌治疗是ERα阳性乳腺癌最重要的辅助治疗手段，ERα是内分泌治疗的重要靶点。前期工作发现乳腺癌抑癌基因RNPC1可以通过其RNA结合功能，直接结合ERα的mRNA，增强ERα mRNA的稳定性从而增强ERα蛋白表达。同时，ERα的过表达可以抑制RNPC1的表达。RNPC1是P53家族的靶基因，并能通过调节其下游靶点表达产生负反馈作用，ERα与P53之间却存在正反馈关系。本项目将明确乳腺癌RNPC1-(P53家族)-ERα轴的精确调控机制：①明确RNPC1通过P53家族间接调控ERα的机制；②明确ERα负反馈调节RNPC1的机制；③明确乳腺癌RNPC1-ERα轴直接/间接途径的功能、发生条件以及综合生物学效应及在内分泌治疗中的意义。从而完善RNPC1对乳腺癌ERα转录后调节机制的理解。本研究的成果将丰富ERα在乳腺癌中的调控机制，为寻找乳腺癌内分泌治疗的新靶点和新策略提供线索。

Endocrine therapy is the most important adjuvant therapy for ERα positive breast cancer. ERα is the key target of endocrine therapy. In previous study,breast cancer suppressing gene RNPC1 could increase ERα expression by stabilizing the mRNA by directly binding to it. On the other hand, overexpression of ERα could repress RNPC1 expression. RNPC1 is the target of P53 family, and forms a negative feedback loop by regulating downstream targets of P53. ERα and P53 family form a positive feedback loop. In this study, we will map the accurate regulating mechanism of RNPC1-(P53 family)-ERα pathway, including: the indirectly way of RNPC1 regulating ERα bypass P53 family; the negative feedback loop between ERα and RNPC1; the function and value of RNPC1-ERα pathway in endocrine therapy of breast cancer. The achievement of this work will modify the understanding of regulating pattern of ERα and promise novel target and strategy of breast cancer endocrine therapy.