The function and mechanism of Nur77 in liver cancer metastasis

核受体Nur77与多种癌症的发展密切相关，包括乳腺癌，结肠癌，胰腺癌等。然而，Nur77在肝癌中的功能却仍不清楚。本课题中，我们发现了Nur77能够通过上调整合素β1的表达，进而促进肝癌细胞的黏附，迁移与侵袭。并且，Nur77也能够诱导整合素β1下游因子的表达，如FAK、paxillin等。FAK-paxillin相互作用在黏着斑形成中发挥着重要作用。我们发现抑制FAK的表达能够逆转Nur77对肝癌细胞迁移和侵袭的促进功能，进一步证明了Nur77调控细胞迁移的下游信号通路。 乙型肝炎x蛋白（HBx）在乙型肝炎病毒（HBV）引起的肝癌中扮演着必不可少的角色。已有报道，HBx能够通过钙蛋白酶促进...Nuclear receptor Nur77 is linked to the development of many types of cancer including breast cancer, colon cancer, pancreatic cancer. However, the function of Nur77 in Hepatocellular carcinoma (HCC) is still unclear. Here we found that Nur77 promotes liver cancer cell adhesion, migration and invasion through upregulating the expression of integrin β1. And Nur77 also induces downstream effectors of...学位：理学硕士院系专业：药学院_化学生物学学号：3232014115339

苯胺嘧啶衍生物X-9通过下调整合素β1表达抑制肝细胞癌迁移侵袭

整合素在许多肿瘤细胞中高表达，并且参与肿瘤细胞的侵袭转移。在肝细胞癌中，整合素β1被报导高表达，并促进肿瘤细胞的侵袭。目前，对于整合素的表达调控癌细胞机制以及干预其表达进而抑制肿瘤细胞转移的研究较少。本研究探讨利用小分子化合物抑制整合素表达来抑制肿瘤细胞迁移和侵袭的可能。首先，对临床肝癌细胞患者癌组织和癌旁组织中的整合素β1的表达进行检测，发现其在癌组织中的表达显著高于癌旁组织（P<0.05）。对TCGA肿瘤数据库的生物信息学分析结果同样显示，整合素β1的高表达与肝癌的分期（P=0.019）和预后（P=0.013）相关。通过筛选发现，苯胺嘧啶衍生物X-9可以抑制肝癌细胞中整合素β1的mRNA和蛋白质的表达（P<0.01）。细胞划痕愈合实验和细胞穿孔结果显示，苯胺嘧啶衍生物X-9能够抑制肝癌细胞的迁移和侵袭（P<0.01）。进一步的研究证实，在肝癌细胞中外源表达整合素β1可以逆转X-9对肝癌细胞迁移和侵袭的抑制；而在敲除整合素β1的细胞中，X-9对细胞的迁移和侵袭的抑制被消除。因此，鉴定出苯胺嘧啶衍生物X-9可以通过下调整合素β1表达，进而抑制肝癌细胞的迁移和侵袭。福建省自然科学基金（No.2016J05087,No.2017J01201）;;福建省卫计委医疗创新项目（No.2015-CXB-15

Amplitude analysis of the decays D0 → π+π−π+π− and D0 → π+π−π0π0*

Using e+e− annihilation data corresponding to an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy √s = 3.773 GeV with the BESIII detector, a joint amplitude analysis is performed on the decays D0 → π+π−π+π− and D0 → π+π−π0π0 (non-η). The fit fractions of individual components are obtained, and large interferences among the dominant components of the decays D0 → a1(1260)π, D0 → π(1300)π, D0 → ρ(770)ρ(770), and D0 → 2(ππ)S are observed in both channels. With the obtained amplitude model, the CP-even fractions of D0 → π+π−π+π− and D0 → π+π−π0π0 (non-η) are determined to be (75.2 ± 1.1stat. ± 1.5syst.) % and (68.9 ± 1.5stat. ± 2.4syst.)%, respectively. The branching fractions of D0 → π+π−π+π− and D0 → π+π−π0π0 (non-η) are measured to be (0.688 ± 0.010stat. ± 0.010syst.)% and (0.951 ± 0.025stat. ± 0.021syst.)%, respectively. The amplitude analysis provides an important model for the binning strategy in measuring the strong phase parameters of D0 → 4π when used to determine the CKM angle γ(φ3) via the B− → DK− decay