PAIP1蛋白在胰腺癌演进中的机制研究

发布时间：2022-08-04 10:51

　　研究背景:胰腺癌（Pancreatic Cancer,PC）是一种高侵袭性、高致命性的恶性肿瘤,具有发病隐匿、缺乏特征性症状等特点,这就决定了该病患者手术切除率低且术后死亡率高。目前,胰腺癌的临床治疗主要以抗代谢药物（如5-氟尿嘧啶、吉西他滨和NAB紫杉醇等）治疗和靶向药物（如贝伐单抗、西妥昔单抗等）治疗为主。在过去的十年中,尽管抗代谢治疗和靶向治疗得到了较好的发展,但由于胰腺癌表型的高侵袭性及其对化疗药物的耐药性等,致使患者的生存率并无明显的改善。因此,深入探究胰腺癌发生发展的分子机制、寻找更为有效的诊断和治疗干预靶点对于改善胰腺癌患者的预后和生存质量具有非常重要的意义。多聚腺苷酸结合蛋白相互作用蛋白 1（Polyadenylate-binding protein-interacting protein 1,PAIP1）是由PAIP1基因（位于5p12）编码的含有479个氨基酸的磷酸腺苷结合蛋白。它可与EIF4A、EIF3结合刺激翻译起始,参与调控细胞的生长、增殖和分化。同时,PAIP1也参与mRNA的稳定--通过与主要蛋白编码区的不稳定性决定因子（MCRD）结合稳定c-fos原癌基... 

【文章页数】：120 页

【学位级别】：博士

【文章目录】：
中文摘要
ABSTRACT
ABBREVIATIONS
1. INTRODUCTION
    1.1 Pancreatic cancer and clinical treatment
    1.2 Poly(A)-binding protein-interacting protein 1
    1.3 AKT signaling pathway in tumor development
    1.4 Epithelial-mesenchymal transition and associated genes
        1.4.1 Epithelial-mesenchymal transition process
        1.4.2 Epithelial-mesenchymal transition markers
            1.4.2.1 EMT marker Vimentin and Snail 1/2
            1.4.2.2 EMT transcriptional factor ZEB 1/ZEB2
            1.4.2.3 EMT marekers Vimentin and E-cadherin
    1.5 Angiogenesis and tumor progression
    1.6 Study design
2. MATERIALS AND METHODS
    2.1 Materials
        2.1.1 Experimental reagents and instruments
    2.2 Methods
        2.2.1 Ethic statement
        2.2.2 Clinical specimens
        2.2.3 Cell culture
        2.2.4 Transfection
        2.2.5 Stable cell line generation
        2.2.6 TCGA BC cohorts
        2.2.7 Cell viability assay
        2.2.8 Colony-forming assay
        2.2.9 Wound healing assay
        2.2.10 Migration assay
        2.2.11 Invasion assay
        2.2.12 Vasculogenic mimicry analysis
        2.2.13 Matrigel tube formation assay
        2.2.14 Chick chorioallantoic membrane assay (CAM assay)
        2.2.15 Immunofluorescence
        2.2.16 Western blot
        2.2.17 Immunohistochemistry
        2.2.18 In vivo tumorigenesis and metastasis assays
        2.2.19 Statistical analysis
3. RESULTS
    3.1 PAIP1 is highly expressed in human PC
    3.2 PAIP1 is correlated with poor prognosis in human PC
    3.3 PAIP1 signficantly promoted the proliferation and colony formation of PC cells
    3.4 PAIP1 promotes the migration, invasion and EMT progression of PC cells
    3.5 PAIP1 promotes angiogenesis in PC cell lines
    3.6 PAIP1 augments PC angiogenesis and invasion potential via AKT pathway activation
    3.7 The overexpression of PAIP 1 promotes tumors growth and metastasis in tumor xenografts
4. DISCUSSION
5. CONCLUSIONS
REFERENCES
攻读博士学位期间取得的科研业绩
致谢



本文编号：3669405