LIN28及let-7调控TGFβ通路在三阴性乳腺癌进展、转移中的作用及机制的研究

三阴性乳腺癌（TNBC）是目前临床治疗效果最差的乳腺癌亚型之一，易发生远处转移而影响患者生存，因此阐明TNBC侵袭及转移分子机制具有重要的理论与实践意义。我们与其他学者的研究发现TNBC细胞内LIN28表达水平显著高于其他亚型乳腺癌且LIN28能增加TNBC细胞的侵袭能力，但其具体机制尚不明了。最近的研究提示TGFβ通路活化水平会影响TNBC的侵袭能力而LIN28及let-7可能会通过直接抑制TGFβRI（直接途径）及通过调控HMGA2抑制TGFβRII（间接途径）调控TGFβ通路。基于此，我们将从三方面开展研究：（一）分析LIN28及let-7是否能改变三阴性乳腺癌细胞的生物学行为。（二）分析LIN28及let-7是否能通过直接和/或间接途径调控TGFβ通路而影响TNBC的运动、侵袭能力及其具体机制。（三）分析TNBC组织标本内LIN28及let-7表达水平是否与患者远期预后存在关联。

Triple negative breast cancer(TNBC) is a special subtype of breast cancer which is known for its invasive biological behavior and poor outcome. Other's and our previous studies found that the expression level of LIN28 was higher in TNBC than other subtypes of breast cancer, which was associated with the invasive behavior of TNBC. Recent results showed that the activation level of TGFβ pathway was associated with the invasive behavior of TNBC and LIN28/let-7 could regulate TGFβ pathway directly by inhibiting TGFβRI or indirectly by inhibiting HMGA2 and TGFβRII. In this study, we will investigate the influence of LIN28 and its target gene and regulator,let-7,on the biologic behavior of TNBC cells. We also will study whether LIN28 and let-7 can regulate TGFβ pathway and thus the biological behavior of TNBC. We will then analyze whether the level of LIN28 and let-7 in the tissue of TNBC can predict the outcome of the patients.